bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics and bioavailability of chloramphenicol in normal and febrile goats*
Authors: KUME BABALE B. , GARG RAMESH C.
Published: April 2008

The effect of induced fever on the plasma concentrations and disposition kinetics of chloramphenicol (CHPC) was studied in adult goats. Fever was induced and maintained for 12 h by injecting Escherichia colt endotoxin (0.1 μ/kg, i.v.) and repeating it at half the dose (0.05 μ/kg) 8 h later. Pharmacokinetics of CHPC was studied in both normal (n= 6) and febrile (n = 6) animals following intravenous administration of CHPC Na‐succinate (25 mg/kg). Intramuscular bioavailability of the drug was also investigated in both normal and febrile animals.

Pharmacokinetics of CHPC following intravenous administration could be described by a two‐compartment open model in both normal and febrile animals. In normal animals the half‐life of CHPC was 73.0 ± 4.95 min and the volume of distribution was 2.217 ± 0.24 1/kg. These and other pharmacokinetic parameters did not differ significantly (P < 0.05) between normal and febrile animals, except for Cop and A. Absorption of CHPC following intramuscular administration was good as indicated by its high bioavailability in both normal (83.34%) and febrile (81.98%) animals.

Volume of distribution is usually expected to change when the febrile state is induced. Lack of such an effect in the present study could be due to high individual variation, or to the fact that CHPC already has a relatively large volume of distribution, which is less likely to be altered by a febrile state of short duration.
An evaluation of apramycin soluble powder for the treatment of naturally acquired Escherichia coli infections in broilers
Authors: CRACKNELL V. C. , ANDREOTIS J. , FACIBENI G. , OWAIS E. , PRADELLA G.
Published: April 2008

During 1983, a series of trials was carried out in Greece, Italy and Jordan, to test the efficacy of the aminocyclitol antibiotic apramycin as a treatment for naturally acquired Escherichia coli infections in broilers. The trials involved a total of 40,389 broilers, 27–39 days of age, in twelve houses at eight different production sites. Three levels of apramycin medication were evaluated: 125, 250 and 500 mg activity/litre drinking water, administered for five consecutive days. Treatment was only initiated after disease had been confirmed by laboratory examination of dead birds. Not all treatments were evaluated in every house. However, each house contained a group of unmedicated birds as controls, while the remaining birds were allocated to one or more apramycin treatment groups.

There was a reduction in mortality and an improvement in the final weight and the economic feed conversion ratio in all three treatment groups. The data presented provide support for the use of apramycin sulphate administered in the drinking water for the treatment of E. coli infections in broilers.
Pharmacokinetics of florfenicol in veal calves
Authors: VARMA K.J. , ADAMS P. E. , POWERS T. E. , POWERS J. D. , LAMENDOLA J. F.
Published: April 2008

Varma, K.J., Adams, P.E., Powers, T.E., Powers, J.D. & Lamendola, J.F. Pharmacokinetics of florfenicol in veal calves. J. vet. Pharmacol. Therap. 9, 412–425.

The pharmacokinetic disposition of florfenicol was described in veal calves after administration of a single 22‐mg/kg dose intravenously, orally after a 12‐h fast and orally 5 min post feeding. Both serum concentrations and urinary excretion were studied. After intravenous administration the median elimination half‐life was 171.9 min while the half‐life of the distribution phase was 5.9 min. The median body clearance (Cl) and apparent volume of distribution (Vz) were 2.85 ml/kg/min and 0.78 1/kg, respectively. Following oral administration the median bio‐availability (f) was 0.88 for calves dosed after a 12‐h fast and 0.65 for calves dosed 5 min post feeding. Calves given the oral doses had a complex absorption pattern with delayed absorption. Slightly more than 50% of the administered dose both orally and intravenously was recovered as unchanged florfenicol in the urine by 30 h.
Pharmacokinetics of antipyrine, acetaminophen and lidocaine in fed and fasted horses
Authors: ENGELKING L. R. , BLYDEN G. T. , LOFSTEDT J. , GREENBLATT D.J.
Published: April 2008

Engelking, L.R., Blyden, G.T., Lofstedt, J. & Greenblatt, D.J. Pharmacokinetics of antipyrine, acetaminophen and lidocaine in fed and fasted horses. J. vet. Pharmacol. Therap. 10, 73–82.

Previous studies demonstrated that plasma clearance of organic anions such as bilirubin, bile acid, sulfobromophthalein (BSP) and indocyanine green (ICG), was reduced from 36% (bile acid) to 55% (ICG) in fasted (3 days) horses. It is believed that a general decline in carrier‐mediated hepatic uptake may have accounted for those changes. However, fasting may also affect hepatic blood flow, thereby contributing to reduced clearance of these compounds. In order to test this hypothesis, plasma clearance of antipyrine, acetaminophen and lidocaine, drugs known to be cleared by the liver yet not suspected of undergoing carrier‐mediated hepatic uptake, were investigated in nine healthy adult mares (three horses/drug group) before and following a 3‐day fast. Results demonstrate that fasting decreased clearance of organic anions from previous studies more than clearance of drugs used in these studies. In addition, clearance of lidocaine, the drug with the highest plasma clearance and therefore the drug most likely to be affected by reduced hepatic blood flow, was affected least by fasting. Therefore, reductions in clearance of these compounds due to fasting must not be due entirely to reductions in hepatic blood flow, but must also involve reductions in intrinsic hepatic clearance.
The effect of magnesium aspartate, xylazine and morphine on the immobilization‐induced increase in the levels of prolactin in turkey plasma*
Authors: ALI B. H. , SILSBY J. L. , HALAWANI M. E. EL
Published: April 2008

Ali, B.H., Silsby, J.L. & El Halawani, M.E. The effect of magnesium aspartate, xylazine and morphine on the immobilization‐induced increase in the levels of prolactin in turkey plasma. J. vet. Pharmacol. Therap.10, 119–126.

The effect of pre‐treating turkey poults (8 weeks old) with magnesium aspartate, xylazine or morphine on the concentration of prolactin (PRL) in plasma was studied in normal birds, and birds stressed with immobilization. Acute immobilization (2 h) without drug treatment increased significantly the PRL concentration in plasma. Pretreatment with magnesium aspartate (405 mg/ml) at intramuscular doses of 100, 200, and 400 mg/bird decreased significantly, in a dose‐dependent manner, the PRL plasma concentration when compared with the immobilized birds. Drug treatment without immobilization had no significant effect on PRL concentration. Similar results were obtained with xylazine (20 mg/ml) when given to birds intramuscularly at doses of 5, 10, or 20 mg/bird, 1 h before immobilization. Morphine, at intramuscular doses of 5 or 10 mg/kg, did not affect significantly the prolactin concentration of immobilized turkeys. At a dose of 25 mg/kg, however, it significantly lowered the PRL plasma concentration in immobilized birds. Morphine treatment alone did not influence significantly the basal PRL plasma concentration.
The pharmacodynamics of the flukicidal salicylanilides, rafoxanide, closantel and oxyclosanide
Authors: MOHAMMED‐ALI N. A. K. , BOGAN J. A.
Published: April 2008

Mohammed‐AH, N.A.K. & Bogan, J. A. The pharmacodynamics of the flukicidal salicylanilides, rafoxanide, closantel and oxyclosanide. J. vet. Pharmacol. Therap. 10, 127–133.

The pharmacokinetics of oxyclosanide, rafoxanide and closantel were investigated in sheep (n = 5). All three drugs were extensively (< 99%) bound to plasma proteins and the plasma concentration/time curve was best described by a tri‐exponential equation. Closantel and rafoxanide had long terminal half‐lives (mean 14.5 and 16.6 days, respectively) compared with oxyclosanide (mean 6.4 days). In a study of the efficacy of rafoxanide against Fasciola hepatica, a dose rate of 7.5 mg kg‐1 against 6‐week‐old flukes appeared to be similarly effective to a dose rate of 2.5 mg kg‐1 against 10‐week‐old flukes (86% and 88% efficacy, respectively), as assessed at autopsies carried out on all sheep when the flukes were 14 weeks old. Part of this putative efficacy against immature flukes may be due to rafoxanide persisting in the plasma and affecting the mature flukes when they reach the bile ducts.
Cardiovascular and respiratory effects of the acaricide amitraz
Authors: CULLEN L. K. , REYNOLDSON J. A.
Published: April 2008

Cullen, L.K. & Reynoldson, J.A. Cardiovascular and respiratory effects of the acaricide amitraz. J. vet. Pharmacol. Therap. 10, 134–143.

Amitraz is a formamidine compound used as a topical acaricide mainly in dogs and cattle. In an initial attempt to explain some of its side‐effects, the actions of amitraz were studied on the cardiovascular and respiratory systems in thiopentone/methoxyflurane‐anaesthetized dogs. In separate experiments, amitraz, at doses of 1, 2 and 5 mg/kg i.v., dissolved in DMSO, increased blood pressure for 1 hour. Heart rate decreased initially then showed a dose‐related return towards control values. Tidal volume, respiratory rate and respiratory minute volume all showed initial transient depression. Hyperventilation was a feature after high doses of amitraz. Cumulative doses of amitraz of 0.5, 1, 2, 5 and 10 mg/kg i.v., at intervals of 5 min, increased blood pressure. Heart rate decreased at lower doses but increased slightly after higher doses. Five minutes after injection, cardiac index had returned to control values while total peripheral resistance showed a dose‐related increase. The mechanism of action of amitraz in dogs cannot be determined from these results; however, other reports have described an ci2‐adrenoceptor agonist action of this formamidine compound.
Actions of non‐steroidal anti‐inflammatory drugs on equine leucocyte movement in vitro
Authors: DAWSON J. , LEES P. , SEDGWICK A. D.
Published: April 2008

Dawson, J., Lees, P. & Sedgwick, A.D. Actions of non‐steroidal antiinflammatory drugs on equine leucocyte movement in vitro. J. vet. Pharmacol. Therap. 10, 150–159.

The direct effects of four non‐steroidal anti‐inflammatory drugs (NSAIDs) on equine polymorphonuclear (PMN) and mononuclear (MN) leucocyte movement were investigated using two in vitro assay systems. The Boyden chamber microfilter technique measures both chemokinetic and chemotactic locomotion, and the agarose microdroplet assay measures solely chemokinesis. Zymosan‐activated plasma (ZAP) and the synthetic peptide N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP) were used as standard chemoattractants for PMN and MN leucocytes, respectively. The actions of six concentrations of each NSAID, indomethacin (50 μM–10 mM), phenylbutazone (10 μM–1 mM), oxyphenbutazone (2.5 μM–500 μM) AND flunixin (0.1 μw–50 μM), in suppressing cell movement induced by ZAP and FMLP were investigated. All four drugs exerted inhibitory effects on induced movement of both cell types in the Boyden chamber assay, usually in a concentration‐dependent manner, although oxyphenbutazone action on PMN cells occurred only at the highest concentration tested. Significant inhibition of PMN and MN cell locomotion was produced by indomethacin, flunixin and oxyphenbutazone, and inhibition of PMN movement by phenylbutazone occurred in the agarose microdroplet assay. Flunixin was the most potent of the four drugs investigated in both assay systems. The findings may be of importance to the use of phenylbutazone and flunixin as NSAIDs in equine medicine, since the concentrations used were similar to concentrations of both drugs and the phenylbutazone metabolite oxyphenbutazone previously reported to occur in equine plasma and inflammatory exudate.
Cardiopulmonary function during 5 hours of constant‐dose isoflurane in laterally recumbent, spontaneously breathing horses
Authors: STEFFEY E. P. , HODGSON D. S. , DUNLOP. C. I. , MILLER M. F. , WOLINER M.J. , HEATH R. B. , GRANDY J.
Published: April 2008

Steffey, E.P., Hodgson, D.S., Dunlop, C.I., Miller, M.F., Woliner, M.J., Heath, R.B. & Grandy, J. Cardiopulmonary function during 5 hours of constant‐dose isoflurane in laterally recumbent, spontaneously breathing horses. J. vet. Pharmacol. Therap. 10, 290–297.

Hemodynamic and respiratory effects of 5 h of unvarying 1.57%, end‐tidal (1.2 MAC) isoflurane in O2 anesthesia were characterized in ten left laterally recumbent horses. Compared to base line values at 30 min of constant dose isoflurane, cardiac output, hematocrit, total plasma solids, PaC02, and peak inspired gas flow progressively and significantly (P < 0.05) increased over the course of study. Arterial blood pressure increased (P < 0.05) during the first 2 h of constant dose of isoflurane then decreased and remained near base line values. Inspiratory time progressively decreased with time of anesthesia. All horses recovered from anesthesia uneventfully within 1 h of termination of isoflurane.
Antinociceptive actions of intravenous a2‐adrenoceptor agonists in sheep
Authors: NOLAN A. , LIVINGSTON A. , WATERMAN A.
Published: April 2008

The antinociceptive activity of the intravenously administered α2‐adrenoceptor agonists, clonidine and xylazine, was measured in sheep using thermal and mechanical pressure threshold detection systems. Both drugs demonstrated clear antinociceptive activity for both forms of threshold stimuli and clonidine at 6 μg/kg i.v. was more potent and longer lasting than xylazine at 50 μg/kg i.v. The antinociceptive effects were reversed by idazoxan (0.1 mg/kg i.v.), but were not affected by naloxone at 0.2 mg/kg i.v. indicating that these effects were mediated by (X2‐adrenoceptors.
Dopamine‐sensitive receptors that evoke rumination and modify reticulo‐ruminal activity in sheep
Authors: STAFFORD K.J. , LEEK B. F.
Published: April 2008

Stafford, K.J. & Leek, B.F. Dopamine‐sensitive receptors that evoke rumination and modify reticulo‐ruminal activity in sheep. J. vet Pharmacol. Therap.11, 171–176.

Dopamine (20 μg/kg) evoked rumination in sheep when injected as a bolus into the coeliac artery or into the left gastric artery but not when injected into the carotid artery. A mixed α‐adrenoreceptor antagonist (phentolamine) and an ci2‐adrenoreceptor antagonist (yohimbine) prevented dopamine from evoking rumination, but a dopaminergic antagonist (metoclopramide) did not. These findings suggest that dopamine stimulated rumination by acting upon ci2‐adrenoreceptors situated in the area supplied by the left gastric artery, whereas dopamine injected intracerebrally may have evoked rumination by an a?‐adrenoreceptor effect in the central nervous system (Bueno et al., 1983) and the actions of intrajugular dopamine were exclusively upon peripheral adreno‐receptors located specifically in the gastric area. Dopamine (1 μg/kg/min) infused into the carotid artery reduced the frequency of reticular contractions by acting upon a centrally located dopaminergic receptor mechanism sensitive to metoclopramide but not to phentolamine. When dopamine was infused into the coeliac artery or into the left gastric artery, the amplitude of reticular contractions was reduced by a peripheral mechanism sensitive both to metoclopramide and to phentolamine. Dopamine also reduced the amplitude of reticular contractions when infused into the carotid artery but to a lesser degree than when given into the coeliac or left gastric artery.
Biphasic disruption of fasting equine gut motility by dopamine – a preliminary study
Authors: N.KING J. , GERRING E.L.
Published: April 2008

King, J.N. & Gerring, E.L. Biphasic disruption of fasting equine gut motility by dopamine; a preliminary study./, vet. Pharmacol. Therap.11, 354–361.

Dopamine was infused intravenously (1,5 and 10 μg/kg/min) for 60 min in three fasted ponies. A dose‐dependent increase in heart rate occurred that was rapid in onset and termination at the start and end of the infusions, respectively. Dose‐dependent changes in gastric and small intestinal motility were observed. An initial marked inhibition of gastric contraction amplitude was followed by a secondary prolonged period of activity. At the same time the small intestine showed a prolonged period of irregular activity (phase II) and a marked increase in the interval between successive phase Ills. The left dorsal colon and small colon exhibited variable responses. The normal fasting motility pattern was therefore disrupted by dopamine biphasically, an initial inhibition of the stomach being followed by a period of increased activity in the stomach and small intestine which resembled the postprandial motility pattern. Although the cardiovascular effects of dopamine were transient, the increases in gastrointestinal motility persisted long after the infusion was terminated.
The effect of the organophosphate trichlorfon on the neuromuscular blocking activity of atracurium in halothane‐anesthetized horses
Authors: HILDEBRAND S. V. , III T. HILL , HOLLAND M.
Published: April 2008

To determine whether cholinesterase inhibition by an organophosphate would influence atracurium's neuromuscular blockade, six horses were anesthetized and paralyzed with atracurium (total of five injections per horse) on experimental Day 1, then were given trichlorfon (64 mg/kg per os) 6 days later. On Day 7, horses were anesthetized and paralyzed in the same manner as on experimental Day 1. Blood was taken to measure serum cholinesterase activity prior to anesthesia on Days 1 and 7. No significant difference was noted in atracurium's neuromuscular blocking activity between the 2 experimental days (P < 0.05), despite Day 7 cholinesterase activity that was 16% of pre‐trichlorfon values. For atracurium Injections 1 and 2–5, 85 and 43 μg/kg of atracurium, respectively, were required to produce a 95–99% reduction in hoof twitch. The time from injection to maximum twitch reduction was approximately 9 min after Injection 1 and 5 min after subsequent injections. Time from injection to maximum twitch reduction was significantly longer for Injection 1 than Injections 2–5 on both experimental days. The time from maximum twitch reduction until 10% recovery was approximately 8 min, with no significant difference between experimental days. The time for twitch recovery from 10 to 75% was approximately 17 min for all injections. Antagonism of atracurium with edrophonium caused the twitch height to return to pre‐atracurium strength in approximately 7 min. Edrophonium caused a significant increase in arterial blood pressure. Heart rate change was variable after edrophonium. Recovery to standing was uneventful for five of the six horses on Day 1, and for all six horses on Day 7. It was concluded that atracurium's neuromuscular blockade was not prolonged by trichlorfon exposure.
Subcutaneously implanted tissue chambers — a pharmacokinetic study
Authors: CLARKE C. R. , SHORT C. R. , BOURNE D. W. A. , USENIK E. A.
Published: April 2008

The purpose of this study was to characterize the pharmacokinetics of a subcutaneously implanted tissue‐chamber model. Thermoplastic tissue chambers were implanted in the paralumbar fossae of six steers. Starting 30 days after implantation, the distribution of intravenously administered antipyrine and phenylbutazone into the tissue chambers was studied. These pharmacokinetic experiments were repeated 10 days later to determine the effect of time after implantation on tissue‐chamber distribution. Fifty days after implantation, tissue chambers were drained of transudate, refilled with sterile saline and the rate of influx of endogenous urea, creatinine and albumin was measured. Delayed diffusion of antipyrine and phenylbutazone into tissue chambers was well described using a compartmental model in which tissue‐chamber fluid represented the third of three compartments arranged in series. The distribution of antipyrine into tissue chambers was greater than that of phenylbutazone; an observation which is well correlated with the high degree of protein binding of phenylbutazone. There was no effect of time on the penetration of the two agents. Rapid diffusion of urea and creatinine and extremely slow influx of albumin into chambers showed that these chambers formed true interstitial compartments.
Spiramycin concentrations in plasma and genital‐tract secretions after intravenous administration in the ewe*
Authors: CESTER C. C. , LAURENTIE M. P. , GARCIA‐VILLAR R. , TOUTAIN P. L.
Published: April 2008

Uterine infections are associated with reduced fertility in ruminant species. Spiramycin is a macrolide antibiotic potentially active against most of the microorganisms isolated from secretions of infected genital tracts. The present work investigated the ability of systemically administered spiramycin to enter genital secretions, by determining the disposition kinetics of the antibiotic in both plasma and uterine genital secretions. Five healthy ovariectomized ewes were given a single intravenous (i.v.) injection of spiramycin, at a dose of 20 mg/ kg. Plasma and genital secretion samples were collected at predetermined intervals for 5 days post‐injection. Blood was collected from the jugular vein while mucus was obtained by inserting polyurethane sponges into the vagina. The spiramycin concentration peak in genital‐tract secretions was obtained 2.53 ±0.63 h after the i.v. administration. The mean residence time was significantly longer (P<0.01) in the mucus (18.31±3.24 h) than in plasma (6.99±2.53 h). An average mucus to plasma ratio of 7.87±3.00 was calculated from the area under concentration‐time curves covering the period under study. These data indicate that after systemic administration to ewes, spiramycin is rapidly found in genital‐tract secretions, at concentrations which are sufficiently high and persistent to suggest its use in the treatment of post‐partum uterine infections.
Effects of haemorrhagic septicaemia vaccination and levamisole administration on the humoral response in cross‐bred calves
Authors: SHARMA L. K. , JAGADISH S. , MULBAGAL A. N.
Published: April 2008

Levamisole administered by oral, subcutaneous or transdermal routes following vaccination against Pasteurella multocida enhanced the humoral response in crossbred calves. The group that received levamisole subcutaneously elicited highly significant (P<0.01) antibody titres during the primary humoral response in comparison with groups that received levamisole orally or transdermally. During the secondary response in the same experiment, levamisole administered subcutaneously and transdermally showed highly significant (P<0.01) haemagglutination titres relative to oral administration of the drug. In a second experiment, the group that received levamisole subcutaneously showed highly significant (P<0.01) antibody titres during the anamnestic humoral response over other treated groups.
Plasma estradiol‐17ß concentrations in the cow during induced estrus and after injection of estradiol‐17ß benzoate and estradiol‐17ß cypionate ‐a preliminary study
Authors: VYNCKIER L. , DEBACKERE M. , De KRUIF A. , CORYN M.
Published: April 2008

Plasma estradiol‐17ß concentrations were investigated in cows during induced estrus and after an intramuscular injection of 10 mg of estradiol‐17ß benzoate and estradiol‐17ß cypionate to determine a withdrawal period for both preparations. After the estradiol‐17ß benzoate injection, the plasma estradiol‐17ß concentration was higher than the physiological maximum of 24 pg/ml obtained during induced estrus for a period of 114±10 h (mean±SEM). For estradiol‐17ß cypionate the corresponding value was 170ß17h (mean±SEM). A withdrawal period of 7 days for the benzoate ester and of 10 days for estradiol‐17ß cypionate is therefore proposed. These results were confirmed by biopsies taken at the injection site 8 and 15 days after the injection of estradiol‐17ß benzoate and estradiol‐17ß cypionate, respectively. In these biopsies no residues of estradiol‐17ß nor of its esters could be detected.
Effect of non‐linear plasma protein binding on unbound and total plasma phenylbutazone concentrations in cows
Authors: BOUDINOT F. D. , WILLIAMS R.J. , SMITH J. A.
Published: April 2008

Boudinot, F.D., Williams, R.J. & Smith, J. A. Effect of non‐linear plasma protein binding on unbound and total plasma phenylbutazone concentrations in cows.J. vet. Pharmacol. Therap.13, 132–136.

The influence of plasma protein binding on unbound and total phenylbutazone concentrations in cows was examined employing data from the literature. Protein binding parameters (number of binding sites and affinity constants) were generated by computer analysis to characterize the concentration‐dependent plasma protein binding of phenylbutazone. Unbound plasma phenylbutazone concentrations were calculated from total plasma drug concentrations observed after administration of a single dose of phenylbutazone to cows. Pharmacokinetic parameters for unbound phenylbutazone were obtained. Parameters characterizing die plasma protein binding and pharmacokinetics of unbound phenylbutazone derived from single‐dose administration were then used to predict unbound and total drug concentrations after multiple‐dose administration of phenylbutazone. Total plasma phenylbutazone concentrations predicted from single‐dose pharmacokinetic parameters agreed well with observed values following multiple‐dose administration of the drug. Thus, the results of this analysis demonstrate that the non‐linear pharmacokinetics of phenylbutazone in the cow can be attributed to the concentration‐dependent plasma protein binding of the drug.

F. Douglas Boudinot, Department of Pharmaceutics, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
The effects of ambient temperature on amikacin pharmacokinetics in gopher tortoises
Authors: CALIGIURI R. , KOLLIAS G. V. , JACOBSON E. , McNAB B. , CLARK C. H. , WILSON R. C.
Published: April 2008

Caligiuri, R., Kollias, G.V., Jacobson, E., McNab, B., Clark, C.H. & Wilson, R.C. The effects of ambient temperature on amikacin pharmacokinetics in gopher tortoises. J. vet. Pharmacol. Therap. 13, 287–291.

The pharmacokinetics of amikacin were compared in two groups of tortoises, one held at 20d̀C and the other at 30d̀C. The mean (± SD) residence time for amikacin in the 30d̀C tortoises was 22.67±0.50 h; significantly (P<0.05) less than those held at 20d̀C (41.83±3.23 h). There was no significant difference (P>0.05) in the steady‐state volume of distribution (Vd(ss)) between the tortoises held at 30d̀C (0.241±0.520 l/kg) and those held at 20d̀C (0.221±0.019 l/kg). The clearance rate was faster (P<0.05) in the warmer tortoises (10.65±2.42 ml/min/kg at 30d̀C compared to 5.27±0.152 ml/min/kg at 20d̀C). These data indicate that while the volume of distribution was approximately the same, amikacin remained in the colder tortoises longer because of its slower elimination. The oxygen consumption and metabolism were measured and found to be lower in the colder tortoises, almost by the same 2:1 ratio as clearance time (Cl), mean residence time (MRT), and area under the curve (AUC). The data derived from this limited study indicated that an appropriate therapeutic dosage regimen for amikacin in gopher tortoises at 30d̀C is 5 mg/kg given i.m. every 48 h.

Dr Randy Caligiuri, University of Florida, College of Veterinary Medicine, Box J‐6 JHMHC, Gainesville, FL 32610, USA.
Investigations into the effect of two sedatives on the stress response in cattle
Authors: BREARLEY J. C. , DOBSON H. , JONES R. S.
Published: April 2008

Brearley, J.C., Dobson, H. & Jones, R.S. Investigations into the effect of two sedatives on the stress response in cattle. J. vet. Pharmacol. Therap. 13, 367–377.

The effects of the sedatives acepromazine (an α‐adrenergic antagonist) and xylazine (an α2‐adrenergic agonist) on plasma indicators of stress in cows were assessed after intramuscular injection and transport. After blood samples had been taken for baseline values, nine cows were given an intramuscular injection of saline (2.5 ml), acepromazine (0.05 mg/kg in 2.5 ml) or xylazine (0.05 mg/kg in 2.5 ml) on different occasions at least 1 week apart. The animals were then transported for 5 min by truck to a different environment and blood sampled for a further 1–3 h. There was a significant increase in plasma Cortisol concentration (3.29 ± 1.59 × baseline) after the injection of saline and transport. The injection of acepromazine also resulted in a significant increase in Cortisol concentration (2.84 ± 0.84 × baseline). There was no similar increase after injection of xylazine. This suggests that α2‐adrenergic receptors are involved in the response of plasma Cortisol concentrations to stressors. An hyperglycaemic response occurred after xylazine (1.66 ± 0.49 × baseline) and saline (1.20 ± 0.1 × baseline) but not after acepromazine. Both sedatives produced a metabolic alkalosis (1.13 ± 0.01 × baseline pH after xylazine and 1.034 ± 0.02 × baseline pH after acepromazine). A greater decrease in haematocrit was seen after both sedatives (0.88 ± 0.04 × baseline after xylazine, 0.81 ± 0.08 × baseline after acepromazine) than after the injection of saline (0.97 ± 0.06 × baseline).

J. C. Brearley, University Department of Anaesthesia, Royal Liverpool Hospital, Prescot Street, PO Box 147, Liverpool L69 3BX, UK.
Pharmacokinetics, safety and tissue residues of sustained‐release sulfamethazine in sheep
Authors: BULGIN M. S. , LANE V. M. , ARCHER T. E. , BAGGOT J. D. , CRAIGMILL A. L.
Published: April 2008

Concentration‐time profiles and the rates of absorption, extent of distribution and half‐lives of sulfamethazine (SMZ), administered intravenously, orally as a water solution and as a sustained‐release formulation (CalfSpanrr̀) were determined in 10 healthy sheep. The geometric mean half‐life of elimination of i.v. SMZ was 10.8 h, compared to 14.3 h for the sustained‐release preparation (CalfSpanrr̀) and 4.3 h for the oral water solution. Blood levels of SMZ were at or above 50 ng/ml for more than 48 h for CalfSpanr̀, for 24 h after i.v. SMZ (100 mg/kg body wt), and for less than 24 h after p.o. SMZ (100 mg/kg body wt). The mean bioavailability of the oral SMZ solution was 58.3% (AUCp.oJAUCi.v). The estimated bioavailability of the CalfSpanr̀ preparation was 52.5%. The safety of the sustained‐release preparation was tested by dosing sheep with multiples (one, three and five times) of the recommended dose (one tablet, 8 g SMZ, per 20 kg body wt), once a day for 3 days. Clinical blood chemistries showed a significant increase in serum iron, and a decrease in serum phosphorus in animals treated at the 3x and 5x dose levels. Necropsies of the 5x dose animals did not show any gross signs that could be attributed to SMZ, and histological examination of tissues from the 5x animals revealed no organ pathology. Residues of SMZ in liver, fat, kidney and skeletal muscle were measured in 20 animals that received one bolus per 20 kg body wt. The results indicate that SMZ residues are cleared rapidly, and are at or below the tolerance level of 0.1 mg/kg within 8 days after dosing so that the 18‐day withdrawal time used in cattle would provide an appropriate margin of safety if used in sheep.
Development of an analytical method for cephapirin and its metabolite in bovine milk and serum by liquid chromatography with UV‐VIS detection and confirmation by thermospray mass spectrometry
Authors: TYCZKOWSKA K. L. , VOYKSNER R. D. , ARONSON A. L.
Published: April 2008

Metabolites of the cephapirin ß‐lactam antibiotic have not previously been reported in bovine milk. The principal metabolite was tentatatively identified as desacetylcephapirin by liquid chromatography with UV‐VIS photodiode array (LC/UV‐VIS PDA), and liquid‐chromatography‐mass‐spectrometric (LC‐MS) detection. Synthetic desacetylcephapirin was prepared by incubation of cephapirin in bovine milk and serum at 37d̀C. Also, a method for determining cephapirin in bovine milk and serum was developed. The detection limits for cephapirin and desacetylcephapirin were estimated to be 10 and 50 ug/kg, respectively, for LC/UV‐VIS PDA, and 100 and 500 ug/kg for LC‐MS.
Pharmacokinetic profiles of netobimin metabolites after oral administration of zwitterion and trisamine formulations of netobimin to cattle
Authors: LANUSSE C. E. , TRUDEAU C. , RANJAN S. , PRICHARD R. K.
Published: April 2008

Pharmacokinetic profiles of the major metabolites of netobimin were investigated in calves after oral administration of the compound (20 mg/kg) as a zwitterion suspension and trisamine salt solution in a two‐way cross‐over design. Blood samples were taken serially over a 72‐h period and plasma was analysed by HPLC for netobimin (NTB) and its metabolites, including albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). NTB was occasionally detected in plasma between 0.5 and 1.0 h post‐treatment. ABZ was not detectable at any time. ABZSO was detected from 0.5‐0.75 h up to 32 h post‐administration, with a Cmaxfor the zwitterion suspension of 1.21 ± 0.13 μg/ml andAUCof 18.55 ± 1.45 μg.h/ml, respectively, which were significantly higher (P < 0.01) than the Cmax(0.67 ± 0.12 μg/ml) andAUC(8.57 ± 0.91 μg.h/ml) for the trisamine solution. ABZSO2was detected in plasma between 0.75 and 48 h post‐administration. The zwitterion suspension resulted in a Cmax(2.91 ± 0.10 μg/ml) andAUC(51.67 ± 1.95 μg.h/ml) for ABZS02, which were significantly higher (P < 0.01) than those obtained for the trisamine solution (Cmax= 1.67 ± 0.11 ug/ml andAUC= 22.77 ± 1.09 ug.h/ml). The ratio ofAUCfor ABZSO2/ABZSO was 2.92 ± 0.26 (zwitterion) and 2.80 ± 0.20 (trisamine). The MRT for ABZSO2was significantly longer (P < 0.01) after treatment with the zwitterion suspension than after treatment with the trisamine solution. There was no apparent difference in t1/2 ß, either for ABZSO (from 5.45 to 5.81 h) or ABZSO2(from 5.16 to 5.93 h) between the two formulations. The oral NTB formulations were not bioequivalent, with the zwitterion suspension giving approximately a twofold higher pharmacokinetic profile (AUC)for ABZSO and ABZSO2than the trisamine formulation.
Disposition of human drug preparations in the horse. I. Rectally administered indomethacin
Authors: DELBEKE F.T , DEBACKERE M. , VYNCKIER L.
Published: April 2008

A high‐performance liquid chromatographic method to measure urinary indomethacin levels is described. In 0.5 ml urine, 1 μg/ml of indomethacin could be detected. Alkaline hydrolysis of urine resulted in the decomposition of indomethacin. When two suppositories of Indocidr̀ corresponding to 200 mg indomethacin were administered rectally to four horses the drug was rapidly absorbed and remained detectable in urine from 1 to 12 h. The excretion rate peaked after 2‐3 h while the maximal concentration ranged from 18.5 to 80.6 μg/ml. Only 8 to 16% of the indomethacin dose was eliminated in urine after 12 h. A fraction of the dose was excreted as the glucuronide conjugate.
Further studies on the antinociceptive activity and respiratory effects of buprenorphine in sheep
Authors: WATERMAN A. E. , LIVINGSTON A. , AMIN A.
Published: April 2008

The thermal and mechanical analgesic profile of buprenorphine at a dose rate of 1.5 μg/kg i.v. was investigated in five sheep. This dose produced significant analgesia for 40 min against the thermal stimulus, bin no mechanical antinocicep‐tion. A higher dose rate of 12 μg/kg also failed to produce anlinociceplion to a mechanical stimulus. In addition, the effect of the drug (6 μg/kg) on respiratory gas tensions was determined and no significant changes were observed.
Pharmacokinetics of tinidazole in dogs and cats
Authors: SARKIALA E. , JÄRVINEN A. , VÄLTTILÄ S. , MERO M.
Published: April 2008

Pharmacokinetics of tinidazole in dogs and cats after single intravenous (15 mg/ kg) and oral doses (15 mg/kg or 30 mg/kg) were studied in a randomized crossover study. Tinidazole was completely absorbed at both oral dose levels in cats and dogs. Peak tinidazole concentration in plasma was 17.8 μ/ml in dogs and 22.5 μ/ml in cats after 15 mg/kg p.o. The oral dose of 30 mg/kg resulted in peak levels of 37.9 μg/ml in dogs and 33.6 μ/ml in cats. The apparent total plasma clearance of the drug was about twofold higher in dogs than in cats, resulting in an elimination half‐life that was twice as long in cats (8.4 h) as in dogs (4.4 h). The apparent volume of distribution was 663 ml/kg in dogs and 536 ml/kg in cats. Therapeutic plasma drug concentrations higher than the MIC values of most tinidazole‐sensitive bacteria were achieved for 24 h in cats and for 12 h in dogs after a single oral dose of 15 mg/kg. From the pharmacokinetic standpoint tinidazole seems to be well‐suited to clinical use in small animal practice.
Comparison of mucosal drug conjugative rates along the gastrointestinal tract of female sheep
Authors: LARRIEU G. , KADDOURI M. , GALTIER P.
Published: April 2008

The comparative distribution of p‐nitrophenol UDP‐glucuronosyl‐transferase, 1‐chloro‐2, 4‐dinitrobenzene glutathione‐S‐transferase and sulphamethazine N‐acetyltransferase activities was studied along the gastrointestinal mucosa of female Lacaune sheep. Gastrointestinal mucosa was characterized by a very low and unequal N‐acetyltransferase activity when activities were expressed per g of wet organ. The duodenum contained highest activities (4.1 nmol/g min). When results were expressed per mg of cytosolic protein, the duodenal activity (0.64 nmol/mg min) was sixfold higher than in liver (0.11 nmol/mg min). There was a lack in N‐acetyltransferase activity accepting isoniazid as substrate. Glucurono‐syltransferase activity was approximately threefold higher in microsomal fractions of the mucosal lining of gastric and colonic intestine (0.43‐0.58 nmol/g min) than in small intestine or caecum (0.10‐0.26 nmol/mg min). Concerning cytosolic glutathione S‐transferase activity, two‐to three fold higher activities were obtained in omasum, jejunum, duodenum and ileum (1021‐2164 nmol/g min) than in other parts (341‐799 nmol/g min) when results were expressed per g of wet organ. These data were compared with corresponding hepatic activities determined in the same six female sheep.
The effects of experimentally induced bronchopneumonia on the pharmacokinetics and tissue depletion of gentamicin in healthy and pneumonic calves
Authors: HUNTER R. P. , BROWN S. ANTHONY , ROLLINS J. K. , NELLIGAN D. F.
Published: April 2008

The effects of a bovine bronchopneumonia model on the pharmacokinetics and tissue residue depletion profiles of gentamicin in calves weighing 90‐140 kg was explored. Two groups of heifer calves were used. The first was a normal group, while the second group had bronchopneumonia induced. A scoring system was developed to evaluate the extent of disease in the groups. A bimodal distribution of the serum pharmacokinetic parameters in the pneumonic group was caused by the effects of dehydration. When the severely dehydrated calves were omitted from the analysis, serum clearance of gentamicin was significantly higher in the pneumonic group than in the normal group (P < 0.05). The pharmacokinetic equations used to fit the tissue concentrations varied from tissue to tissue and between groups. Because the best equation of a particular tissue's concentrations varied between groups, withdrawal periods, which are normally determined in healthy animals, may be inappropriate in diseased animals. Addition of several parameters (serum creatinine, serum urea nitrogen, albumin, fibrinogen, and total protein concentrations, white blood cell counts, central iluid volume, volume of distribution at steady state, area under the serum concentration vs time curve, serum clearance, and elimination rate constant) to these tissue‐depletion models using multiple regression improved the prediction of a concentration in a given tissue.
Pharmacokinetic and tissue distribution study of oxytetracycline in rainbow trout following bolus intravenous administration
Authors: BLACK W. D. , FERGUSON H. W. , BYRNE P. , CLAXTON M. J.
Published: April 2008

Oxytetracycline pharmacokinetics and tissue distribution were studied in rainbow trout following bolus i.v. administration at 5 mg/kg. The mean serum (log) drug concentration data were plotted against time (linear). The decay curve was described by a three‐component exponential decay function and a three‐compartment model. The t1/2 of rapid distribution was 0.9 h, the t1/2 of the slow distribution was 5.9h and the t1/2 elimination was 81.5 h. Clearance was 25.4 ml/kg/h and Vd(area) 2988 ml/kg. Regression analysis of the serum levels for the three intervals, 0.5‐2.0 h, 6.0‐18.0 h, and 24‐96 h, indicated that the rates of decay for each interval were 0.6151 h‐1, 0.0564 h‐1 and 0.0088 h‐1 respectively. Rates of equilibration between tissues and serum were determined. Kidney equilibrated the fastest with t1/2 to equilibration of 1.1h for H (anterior) kidney and 1.98h for P (posterior) kidney. The highest drug levels were found in the liver and the lowest were in the brain.
Furosemide‐induced changes in plasma and blood volume of horses
Authors: HINCHCLIFF K. W. , McKEEVER K. H. , MUIR W. W.
Published: April 2008

The effect of furosemide administration (1mg/kg body weight, i.v.) on plasma and blood volumes in 6 intact and 4 splenectomized horses was measured using Evans blue dye dilution, hematocrit, and hemoglobin and plasma total solids concentrations. Body weight decreased by 33.6±3.3 and 33.7±0.8g/kg 4h after furosemide administration to intact and splenectomized mares, respectively. Plasma volume, estimated by Evans blue dye dilution, was reduced by 8.3±3.3% (mean±SE) 4h after furosemide administration. The reduction in plasma volume was first detectable 5‐10 min after furosemide administration and was greatest 15‐30 min (13.0±0.8%) after dosing. This study demonstrates that furosemide produces significant and rapid reductions in plasma volume in horses. These decreases in plasma volume only partially resolve 4h after furosemide administration.
Modification by 6‐hydroxydopamine (6‐OHDA) of the inhibition of extrinsic rumen contractions in sheep produced by beta‐endorphin
Authors: KANIA B. F. , VAN MIERT A. S. J. P. A. M.
Published: April 2008

In sheep, beta‐endorphin (1 and 2 μg/kg) administered into the third cerebral ventricle caused a significant inhibition of the frequency of rumen contractions. The amplitude of the first rumen contractions, following immediately after the end of infusion, and the average amplitude of primary rumen contractions, were inhibited. Beta‐endorphin caused general psychomotor excitability. These results suggest that an inhibitory p and 6 opioid system is involved in the control of forestomach motility and general behaviour in sheep. All effects of beta‐endorphin were completely prevented by i.c.v. 6‐hydroxydopamine (6‐OHDA, 18.2 μg/kg) pre‐treatment. These results suggest that beta‐endorphin‐induced inhibition of rumen motility is due to central noradrenergic system activation. The exact location of this noradrenergic system remains to be determined.
Pharmacokinetics of levamisole in rabbits after intravenous administration
Authors: GARCÍA J. J. , DIEZ M. J. , SIERRA M. , TERÁN M. T.
Published: April 2008

A compartmental and non‐compartmental pharmacokinetic study was carried out on rabbits after intravenous (i.v.) administration of levamisole at the three dose rates: 12.5, 16.0 and 20.0 mg/kg body weight. Using compartmental analysis, the disposition of levamisole best fitted a two‐compartmental open model with mean values of α= 0.1278, 0.1019 and 0.1282 min‐1; β= 0.0139, 0.0126 and 0.0124 min‐1; A= 0.24, 5.27 and 10.58 μg/ml and B= 2.14, 3.83 and 5.08 μg/ml for each dose, respectively. The statistical moment theory was mainly used for non‐compartmental analysis. Values for mean residence time (MRT) of 69.2, 71.7 and 73.1 min were obtained for each dose. The mean values for volume of distribution at steady stale (Vd(SS)), determined by compartmental analysis, were 3879, 3279 and 2735 ml/kg for each dose, and values obtained using the statistical moment theory were 3760, 3015 and 2943 ml/kg; there were no statistically significant differences using Student's paired t‐test. Identical conclusions were obtained using both methods when the parameters β, AUC and Cl were compared.
Formulation and (bio)availability problems of drug formulations in birds*
Authors: DORRESTEIN G. M.
Published: April 2008

Most drugs used for the treatment of birds are not formulated for birds. Therefore the availability of drugs for birds and their administration routes largely depend on formulations available for man, mammals and to some extent poultry. The problems with the application of existing formulations, the drug concentrations and the many different avian species are discussed.

The desire of the avian veterinarian for the combination of several active compounds presents special problems. This again requires extra data on the interactions in galenic, pharmaceutic, pharmacokinetic and dynamic phases, which are generally not readily available.
Bioavailability and bioinequivalence of drug formulations in small animals*
Authors: WATSON A. D. J.
Published: April 2008

Differences in bioavailability of many drugs from their various dosage forms have been shown to be relatively common in human medicine. Although comparable bioavailability (‘bioequivalence’) is thought to ensure comparable clinical effectiveness and safety (‘therapeutic equivalence’), the relationship between bioinequivalence and therapeutic inequivalence is less clear. Thus the prevalence of clinically important differences in bioavailability is unknown. While similar concerns have arisen about drug products used in small animal practice, there have been few investigations and some earlier reports are incomplete. However, there are indications of bioinequivalence with enteral formulations of ampicillin, aspirin, chloramphenicol, digoxin, rnitotane, oxytet‐racycline, penicillin V and theophylline. Other studies have suggested bioequivalence with enteral formulations of chloramphenicol, digoxin, phenytoin, oxytetracycline and thyroxine. Limited data for injectable preparations showed bioinequivalence with chloramphenicol and possibly oxytetracycline. There is no reason to expect formulation‐related bioinequivalence to be less prevalent in veterinary than in human medicine. Indeed, it may be more common in veterinary practice because other potential influences on bioavailability (food, diseases, other drugs, etc.) are frequently ignored, and cheaper generic products are often favoured for economic reasons.
Bioavailability and bioequivalence of veterinary drug dosage forms, with particular reference to horses: an overview*
Authors: BAGGOT J. D.
Published: April 2008

The route of administration and formulation of the dosage form affect the bioavailability (rate and extent of absorption) of a drug and may thereby influence the intensity and duration of the pharmacological effect. Location of injection site may affect the plasma concentration profile of drugs administered as aqueous suspensions or sustained release potential preparations (procaine penicillin G). When absorption influences the rate of elimination (‘flip‐flop’ phenomenon), the apparent half‐life of the drug will be increased (cefazolin sodium, i.m.; meclofenamic acid, p.o.).

Absorption generally approximates a first‐order process and either the absorption half‐life or the mean absorption time (statistical moment term) will provide an estimate of the rate of absorption. The method of corresponding areas is the usual technique employed in estimating the extent of absorption (systemic availability). Inherent in this technique is the assumption that clearance of the drug remains unchanged. In horses, the time of feeding relative to oral dosing has been shown to affect systemic availability (rifampin, trimethoprim) and pattern of absorption (phenylbutazone). Oral paste formulations (trimethoprim‐sulphadiazine, ivermectin) are convenient to administer, allow precision in dosage compared with powders or granules added to feed, and could provide sustained release.

Assessment of bioequivalence is based on relative bioavailability, using a reference dosage form, together with a measure of the uncertainty (variance) of the estimate. Bioequivalence relies on the concept that preparations of a drug which provide essentially equivalent plasma concentration profiles should produce the same therapeutic effect.