bluuebunny/crossref_metadata_2025_split huggingface dataset:
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.
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.
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.
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 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.
Pharmacokinetic–pharmacodynamic modelling of meperidine in goats (I): pharmacokinetics
Authors: QIAO G.‐L. , FUNG K.‐F. 
Published: April 2008

Qiao, G.‐L., Fung, K.‐F. Pharmacokinetic‐pharmacodynamic modelling of meperidine in goats (I): pharmacokinetics. J. vet. Pharmacol. Therap. 16, 426–437.Plasma and cerebrospinal fluid (CSF) pharmacokinetics of meperidine were investigated after intramuscular (i.m.) or intravenous (i.v.) administration at a dose of 5 mg/kg in adult goats. After i.m. dosing, the plasma profile was best described by a one‐compartment open model. In healthy (n = 16) and postoperative (n = 16) goats, the parameters were, respectively: /max 8.3 ± 3.9 and 9.2 ± 5.5 min, Vd 2.763 ±1.231 and 3.929 ±2.101 1/kg, Clb 0.125 ± 0.036 and 0.087 ± 0.025 1/kg/min, Kc 0.0563 ± 0.0358 and 0.0271 ± 0.0136 min‐1. The plasma profile was best fitted by a two‐compartment open model following i.v. injection. In this case, the parameters for healthy (n= 7) and post‐operative (n= 13) goats were, respectively: Vd 5.212 ± 1.992 and 5.085 ± 2.288 1/kg, Clb 0.096 ± 0.028 and 0.075 ± 0.026 1/kg/min, P 0.0211 ± 0.0093 and 0.0160 ± 0.0052 min.‐1. There were, however, a few individuals with a prolonged elimination phase. Bioavailability of i.m. meperidine was 66.5 ± 15.8% in healthy (n= 6) goats, but much higher in postoperative (n = 10) ones at 94.6 ± 30.0%. Meperidine diffused into and out of CSF according to a first‐order rate process. The time‐course of CSF drug concentration was simulated by a biexponential function. CSF kinetic parameters of i.m. meperidine for healthy (n = 7) and postoperative (n = 13) goats were: elimination rate constant (Kei) 0.0269 ± 0.0131 and 0.0305 ± 0.0177 min“1, peak CSF concentration time (Tnaxl) 15.9 ± 5.0 and 17.0 ± 6.9 min. For the i.v. dosed healthy (n = 6) and postoperative (n = 8) animals, Kel was 0.0408 ± 0.0107, 0.0414 ± 0.0123 min‐1 and 7maxt was 10.0 ± 5.0 and 7.7 ± 2.5 min, respectively. It was demonstrated that an obviously lower peak concentration can be reached significantly later in CSF than in plasma, and the kinetic behaviour of meperidine in plasma is different from that in the CSF, indicating meperidine analgesia might not be predicted by simple extrapolation from the kinetic data.
Sulfadimidine metabolism in vitro: II. comparative studies in cultured rat, goat, sheep and cattle hepatocytes
Authors: KLOOSTER G. A. E. VAN T , BLAAUBOER B.J. , NOORDHOEK J‐ , MIERT A. S.J. P. A. M. VAN 
Published: April 2008

van't Klooster, G.A.E., Blaauboer, B.J., Noordhoek, J. & van Miert, A.S.J.P.A.M. Sulfadimidine metabolism in vitro: II. comparative studies in cultured rat, goat, sheep and cattle hepatocytes. J. vet. Pharmacol. Therap. 16, 454–461.Hydroxylation and acetylation of sulphadimidine (SDD) and the deacetylation of N4‐acetyl SDD was investigated in cultured hepatocytes from male and female rats, from male and female goats and from female sheep and cattle. Significant sex differences were observed for hydroxylation of SDD in hepatocytes from rat and goat. In goat, sheep and cow hepatocytes, the hydroxylation pathway is relatively important, whereas in rat hepatocytes, acetylation is predominant. Hepatocytes of all four species deacetylated N4‐acetyl SDD. In ruminant hepatocytes, deacetylating activity was of considerable importance, whereas in rat hepatocytes, it appeared a minor pathway of metabolism. Similar to thein vivosituation, formation of N4‐acetyl SDD in cultured hepatocytes results from an equilibrium of acetylation and deacetylation. A good correlation was found between results in isolated hepatocytes and previous findingsin vivo, both in levels of species‐related activities and in acetylation‐hydroxylation ratios. In conclusion, cultured hepatocytes appear a usefulin vitromodel to study comparative sulfonamide metabolism.