bluuebunny/crossref_metadata_2025 huggingface dataset:
Morantel tartrate release from a long‐acting intraregional device in cattle: pharmacokinetics and gastrointestinal distribution
Authors: LANUSSE C. E. , GASCON L. H. , RANJAN S. , PRICHARD R. K.
Published: April 2008

The pharmacokinetics and gastrointestinal distribution of ornately tart rate release from a sustained release trilaminate bolus in cattle were investigated over a 98‐day period post treatment. Six Holstein calves (125–150 kg) had permanent indwelling fistulae surgically inserted into the rumen, abomasum and terminal ileum. Samples of jugular blood, feces and ruminal, abomasal and ileal fluids were taken on days ‐3, 1, 4, 7, 10, 14 and weekly up to 98 days post‐bolus administration. Morantel tartrate concentrations were measured by HPLC after extraction and clean‐up. Morantel was not detected in plasma at any time after bolus administration. High concentrations of morantel tartrate were found in ruminal, abomasal and ileal fluids and feces over 98 days post‐treatment. The morantel peak concentration (Cmax) was achieved at Day 1 post‐administration in each of these compartments. The steady‐state morantel concentration (Css was achieved at approximately 10 days post‐treatment and maintained for 91–98 days post‐treatment in these gastrointestinal compartments. The morantel Cmax Css, area under the zero (AUC) and first moment (AUMC) of the concentration‐time curve were significantly higher (P < 0.01) in feces than in other compartments. The in vivo drug release profile of this device has been determined. Steady‐state concentrations for from 91 to 98 days have been confirmed.
Pharmacokinetics and intramuscular bioavailability of amikacin in chickens following single and multiple dosing
Authors: EL‐GAMMAL A. A. , RAVISt W. R. , KRISTA L. M. , TOLBERT D. S. , SAAD A.
Published: April 2008

The pharmacokinetics of amikacin were studied in healthy mature female chickens (n =6). Single doses of amikacin were injected as an i.v. bolus (10 mg/ kg) and im. (20 mg/kg) into the same birds with a 30‐day rest period between treatments. Amikacin was determined by the fluorescence polarization im‐munoassay method. The i.v. pharmacokinetics could be described by a two‐compartment model with a t1/2αof 0.150 ± 0.064 h and a t1/2βof 1.44 ± 0.34 h. The total body clearance was 0.109 ± 0.017 l/h/kg and the volume of distribution at steady‐state was 0.193 ± 0.060 Vkg. Following a single i.m. injection. the peak plasma concentration (Cmax) was 50.79 ± 4.05 μg/ml and occurred at 0.50 ± 0.26 h. The i.m. extent of absorption was 91.2 ± 17.65%. Simultaneous modeling of i.v. antl i.m. results provided estiinates of an absorption half‐life of 0.480 ± 0.158 h.

The i.m. pharmacokinetics after repeated administration were stittlied following the tenth close (20 mg/kg, every 8 h). The Cssmaxwas 38.58 ± 6.96 pgi nil and occurred at 0.79 ± 0.37 11, and the biological half‐life of aniikncin was 1.86 5 0.47 11. The multiple closing yielded peak concentrations of 39 μg/ml and trough concentrations of 3.26 μg/ml. Based on these data, the recomnienclecl amikacin dosage in chickens is 20 mg/kg body weight every 8 h.
Prescribing of drugs for food‐producing animals in Norway. Information about withdrawal times
Authors: BANGEN M. , SKJERVE E. , GRAVE K. , SØLI N. E.
Published: April 2008

The prescribing of drugs for food‐producing animals in Norway was investigated with special emphasis on written information given about withdrawal times. The study was designed as a cross‐sectional prescription survey.

Of 1518 prescriptions for food‐producing animals, it was concluded that 1224 of the prescriptions were for drugs requiring withdrawal times for meat, milk or eggs. Of these 1224 prescriptions, 82.8% were for veterinary preparations, 6.6% were for human preparations and 10.6% were for other drugs.

For 20.8% of the prescriptions, information about withdrawal time(s) was missing. For prescriptions for veterinary preparations this figure was 5.9%, and for prescriptions for human preparations and other drugs 95.1% and 90.8%, respectively. For veterinary preparations approved for the intended species, as many as 99.2% gave information about withdrawal times on the drug container label.

Lack of information about withdrawal times might give rise to drug residues in food for human consumption and thus pose a potential hazard to human health.
Effect of erythromycin on L‐threonine transport in rabbit jejunum in vitro
Authors: NAVARRO H. , ARRUEBO M. P. , SORRIBAS V. , ALCALDE A. I.
Published: April 2008

Several antibiotics characterized by different molecular structures are known to affect some intestinal activities. Some of them have been described as inhibitors of the intestinal sugar and amino iced transport with different mechanisms. Erythromycin (EM) is a rnacrolide antibiotic acting as a motilin agonist and thus stimulating the gastrointestinal motor activity. Since several substances which increase the motor activity of the gastrointestinal tract may produce effects on the intestinal absorption of nutrients, the present study has been carried out to determine whether erythromycin affects the L‐threonine intestinal absorption. The results obtained indicate that erythromycin diminishes the L‐threonine intestinal transport, probably at the mucosal border level. Two groups of experiments carried out, with Na+‐deprived medium and ouabain‐enriched medium, might indicate that erythromycin action could be due to either a direct or an indirect action on the Na+‐dependent r‐threonine transport located in the brush border.
Mathematical description of the concentration of Oxytetracycline and penicillin‐G in tissue cages in calves as related to the serum concentration
Authors: BENGTSSON B. , BREDBERG U. , LUTHMAN J.
Published: April 2008

A mathematical model based on Fick's laws of diffusion describing the concentration of drug in tissue cage models was elaborated. The model takes into account differences in protein binding, tissue cage geometry and serum pharmacokinetics. The validity of the model was tested against experimental data obtained from a tissue cage model in calves by simultaneous fitting to serum and tissue cage fluid (TCF) data in a non‐linear least‐squares regression computer program. Concentrations of penicillin‐G (pen‐G) in serum and TCF following intravenous (i.v.) administration of potassium pen‐G were adequately described by the mathematical model. Concentrations in TCF after intramuscular (im.) administration of the same drug and of procaine pen‐G could be predicted by the mathematical model. Concentrations of oxytetracycline (OTC) in serum and TCF following i.v. administration and continuous i.v. infusions were also adequately described by the model, and TCF concentrations after i.m. administration of the same drug could be roughly predicted. The results indicate that pen‐G and OTC have the same permeability coefficient for transport from serum to TCF.
Effects of phenothiazine and thiabendazole on bovine dorsal pedal vein contractility induced by ergonovine and serotonin; Potential for alleviation of fescue toxicity
Authors: OLIVER J. W. , ROBINSON A. J. , ABNEY L. K. , LINNABARY R. D.
Published: April 2008

Phenothiazine and thiabendazole were studied for their ability to antagonize venoconstriction induced by ergonovine, and the biogenic amine serotonin, in the isolated dorsal pedal vein of cattle. The two compounds are commercially available, approved for usage in cattle and have been reported to reverse some of the toxic effects associated with the intake of Acremonium coenophialum‐infested fescue forage by cattle. Neither compound had any antagonistic activity against venoconstriction induced by ergonovine. However, thiabendazole did have some activity against venoconstriction induced by serotonin. Ergot alkaloids are known to cause venoconstriction through effects on biogenic amine receptors, including serotonergic receptors, and since thiabendazole has anti‐serotonin activity, part of the reported beneficial effects of thiabendazole in alleviating fescue toxicity may be due to the anti‐serotonin activity of the drug. Further work is needed to determine if phenothiazine and thiabendazole have any effect on other types of alkaloids that are present in A. coenophialum‐infested fescue.
Methimazole‐mediated modulation of netobimin biotransformation in sheep: a pharmacokinetic assessment
Authors: LANUSSE C. E. , GASCON L. , PRICHARD R. K.
Published: April 2008

The effects of modulation of liver microsomal sulphoxidation on the disposition kinetics of netobimin (NTB) metabolites were investigated in sheep. A zwitterion suspension of NTB was given orally at 7.5 mg/kg to sheep either alone (control treatment) or co‐administered with methimazole (MTZ) orally (NTB + MTZ oral treatment) or intra‐muscularly (NTB + MTZ i.m.) at 3 mg/kg. Blood samples were taken serially over a 72 h period and plasma was analysed by HPLC for NTB and its major metabolites, i.e. albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2). Only trace amounts of NTB parent drug and ABZ were detected in the earliest samples after either treatment. There were significant modifications to the disposition kinetics of ABZSO in the presence of MTZ. ABZSO elimination half‐life increased from 7.27 h (control treatment) to 14.57 h (NTB + MTZ oral) and to 11.39 h (NTB + MTZ im.). ABZSOAUCswere significantly higher (P < 0.05) for the NTB + MTZ oral treatment (+55%) and for the NTB + MTZ i.m. treatment (+61%), compared with the NTB alone treatment. The mean residence times for ABZSO were 12.66 5 0.68 h (control treatment), 18.85 ± 2.35 h (NTB + MTZ oral) and 17.02 ± 0.90 h (NTB + MTZ im.). There were no major changes in the overall pharmacokinetics of ABZSO2for the concomitant MTZ treatments. However, delayed appearance of this metabolite in the plasma resulted in longer ABZSO2lag times and a delayed Tmaxfor treatments with MTZ. We have demonstrated that co‐administration of MTZ, both orally and intra‐muscularly, results in an altered pharmacokinetic pattern for the metabolites of NTB. The changed pharmacokinetic profile of the anthelmintically‐active ABZSO metabolite may result in enhanced efficacy.
Vancomycin kinetics in plasma and synovial fluid following intravenous administration in horses
Authors: ORSINI J. A. , RAMBERG C. F. , BENSON C. E. , DREYFUSS D. J. , VECCHIONE J. A. , KUNZ C. C.
Published: April 2008

Vancomycin hydrochloride was infused intravenously (i.v.) over a 30‐min period in five horses at doses of 6.6, 11.0 and 15.4 mg/kg. Vancomycin concentration in plasma and synovial fluid samples was measured using a polarization immunoassay. A pharmacokinetic model was developed to accommodate the special features of the present study. The data were described by a two compartment open model with synovial fluid as an additional compartment in exchange with plasma. Minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) were measured for Staphylococcus aureus and Enterococcus sp. using isolates from hospital patients. Based on the pharmacokinetic model and MIC/MBC data, a practical therapeutic protocol for vancomycin administration was established at doses of 4.3–7.5 mg/kg given as a 1‐h infusion every 8 h.
Evaluation of antibiotics for racing pigeons (Columba livia var. domestica) available in The Netherlands
Authors: ZWIJNENBERG R. J. G. , VULTO A. G. , VAN MIERT A. S. J. P. A. M. , LUMEIJ J. T.
Published: April 2008

Antibiotics and chernotherapeutics marketed for use in racing pigeons (Columba livia var. domestica) were evaluated by comparing the dosages and indications given by the manufacturers with the data obtained by pharmacokinetic, bacteriological and efficacy studies. This comparison showed that only three of the recommended dosages and indications of the 60 formulations marketed in The Netherlands are scientifically sound and in accordance with the literature. It is to be expected that the majority of the antimicrobials for pigeons will not satisfy the requirements for final registration as a pigeon therapeutic under the Dutch Veterinary Medicines Act of 1985. Several factors affecting drug availability are discussed, such as the different routes of administration and the influence of food. The public health aspects of the consumption of medicated pigeons is also discussed. Although there is no legislation with regard to this subject, a recommended withdrawal time of 10 days for the majority of the antimicrobials seems advisable.
Evaluation of anthelmintics, antiprotozoal drugs and ectoparasiticides for racing pigeons (Columba livia var. domestica) available in The Netherlands
Authors: ZWIJNENBERG R. J. G. , VULTO A. G. , VAN MIERT A. S. P. J. A. M. , LUMEIJ J. T.
Published: April 2008

Anthelmintics, antiprotozoal drugs and ectoparasiticides specially marketed for use in racing pigeons (Columba livia var. domestica) were evaluated by comparing dosages and indications given by the producers with data obtained from efficacy studies or empirical data. Of a total of 63 products, 59% were in accordance with the literature. Fifty‐nine percent of the dosages and indications of anthelmintics were in accordance with scientifically obtained data, while for trichomonacides, coccidiostats and ectoparasiticides the figures were 47%, 59% and 100% respectively. Public health aspects of the consumption of medicated pigeons are discussed.
Effect of water deprivation on absorption (oral, intramuscular) and disposition of ampicillin in sheep
Authors: OUKESSOU M. , TOUTAIN P. L.
Published: April 2008

The effects of a 72 h water deprivation on the absorption — intramuscular (i.m.) and oral and disposition of ampicillin, inulin and para‐aminohippuric acid (PAH) were investigated in six sheep. After intravenous (i.v.) administration of ampicillin sodium (10 mg/kg), the water deprivation decreased slightly the initial volume of distribution (0.082 ± 0.033 vs. 0.055 ± 0.030 l/kg) but not the steady state volume of distribution. The plasma clearance was significantly decreased (6.21 ± 1.94 vs. 3.90 ± 1.92 ml/min/kg) and the mean residence time (MRT) was increased from 22.25 ± 4.91 to 33.36 ± 8.16 min. After i.m. administration of ampicillin sodium (20 mg/kg), ampicillin concentrations were systematically higher after a 3‐day period of water deprivation than during the control period but the muscular absorption rate was not modified. After oral administration of ampicillin trihydrate (1 g in toto) plasma concentrations were much lower and more persistent than after an i.m. administration and the systemic availability remained low whatever the hydration status. Influences of water deprivation on ampicillin disposition were linked to adaptation of renal function as assessed by inulin and PAH clearances. The therapeutic relevance of the results are discussed for a better definition of dosage regimens for sheep reared in arid environments.
Pharmacokinetics of single intravenous and single and multiple dose oral administration of rifampin in mares
Authors: KOHN C. W. , SAMS R. , KOWALSKI J. J. , POWERS J. , WALLACE S.
Published: April 2008

The disposition of rifampin in six healthy mares after single intravenous (i.v.) and oral (p.o.) doses and after seven oral doses of 10 mg/kg administered twice a day was investigated using a high performance liquid chromatographic (HPLC) method. Pharmacokinetic variables for rifampin determined using the HPLC method were comparable to variables reported from earlier studies utilizing a microbiological assay. Desascetylrifampin, a major metabolite of the parent compound, could not be detected in the serum but was detected at low concentrations in urine. Mean trough concentrations of rifampin increased from the first to the second dose of the multiple dose oral study and then remained unchanged through 72 h. At 84 h after the first dose (i.e. 12 h after the final dose) the rifampin concentration was significantly decreased (P= 0.001). The harmonic mean of the half‐life of rifampin decreased significantly from 13.3 h after a single oral dose of 7.99 h after the seventh oral dose. The mean serum protein binding of rifampin over the concentration range of 2–20 μg/ml was 78%. Mean trough serum concentrations of unbound rifampin after multiple oral doses ranged from 0.67 μg/ml at 24 h to 0.40 μg/ml at 72 h. The mean unbound serum rifampin concentration at 84 h (i.e., 12 h after the final dose) was 0.30 μg/ml. Trough concentrations and the 84‐h sample concentration of unbound rifampin exceeded the minimum inhibitory concentration for most gram positive bacterial isolates from horses reported in this study. All organisms with minimum inhibitory concentrations less than 0.125 μg/ml were considered susceptible.

Based on the pharmacokinetics of rifampin after p.o. administration, we concur with the current dosage recommendation of 10 mg/kg twice a day by mouth. At this dose, most streptococci,Rhodococcus equi, and coagulase‐positive staphylococci would be considered susceptible to rifampin.
The effect of age on phenylbutazone pharmacokinetics, metabolism and plasma protein binding in goats
Authors: ELTOM S. E. , GUARD C. L. , SCHWARK W. S.
Published: April 2008

Phenylbutazone (PBZ) was administered intravenously as a single dose (10 mg/ kg) to adult male and 1‐day‐, 10‐day‐, 4‐week‐ and 6 week‐old male goats. The plasma concentration of PBZ and its major metabolites oxyphenbutazone (OPBZ) and γ‐hydroxyphenbutazone (γ‐OHPBZ) was measured over time. The elimination half‐life (t½β) of PBZ decreased from 120 h in the 1‐day‐old to 16 h in the adult goats. Although the volume of distribution (Vd) did not change significantly during maturation, the total body clearance (ClB) increased from 2 ml.h‐1.kg‐1in I‐day‐old t o 13 ml.h‐1.kg‐1in the adult goats; the increase was 2‐fold in the first 10 days of life. Oxyphenbutazone was detectable in the plasma of adult and 6‐week‐old goats as early as 15 min after PBZ administration. Its peak concentration occurred at 1.5 h (1.6 μg/ml) in adults and at 6 h (0.95 μg/ml) and 12 h (0.36 μg/ml) in 6‐ and 4‐week‐old goats respectively. The highest plasma concentration of γ‐OHPBZ was achieved in 4‐week‐old followed by 6‐week‐old and adult animals.
Comparative kinetic disposition of oxfendazole in sheep and goats before and during infection with Haemonchus contortus and Trich ostrongylus colubriformis
Authors: HENNESSY D. R. , SANGSTER N. C. , STEEL J. W. , COLLINS G. H.
Published: April 2008

The kinetic disposition of [14C]‐oxfendaEole (OFZ) and its metabolites, fenben‐dazole (FBZ) and fenbendazole sulphone (FBZ.SO2), in plasma and abomasal fluid were determined in Merino sheep and Angora goats before and during infection with Trichostrongylus colubriformis and Haemonchus contortus. The systemic availability (area under the plasma curve, AUC) of OFZ was significantly lower in goats (13.5 μg.h/ml) than in sheep (22.2 μg.h/ml) and was reduced with infection in goats (5.6 μg.h/ml) and sheep (15.1 μg.h/ml). The elimination of plasma [l4C] was faster in goats than in sheep. The responses observed for [14C] were a reflection of the behaviour of OFZ. The concentration of OFZ and metabolites in abomasal fluid were similar in both species in the absence or presence of infection. However, as the mean flow rate of abomasal fluid was slower in goats (240 ml/h) than in sheep (488 ml/h), only 7% of the dose passed the pylorus in abomasal fluid of goats compared with 14% in sheep. The presence of gastrointestinal nematodes generally increased abomasal fluid flow rate but neither species nor infection had any effect on the rate or extent of [14C] excretion in urine or faeces. It is suggested that goats possess a faster hepatic metabolism than sheep resulting in more rapid elimination of OFZ.
Plasma salicylate concentrations in immature dogs following aspirin administration: comparison with adult dogs
Authors: WATERS D.J. , BOWERS L. D. , CIPOLLE R. J. , CAYWOOD D. D. , BILL R. L.
Published: April 2008

Aspirin disposition in immature and adult dogs, assessed by plasma salicylate concentrations following single doses of aspirin given orally (p.o.) and intravenously (i.v.), was compared. Using a cross‐over design, four immature (12–16‐weeks‐old) and eight adult (1– 2‐years‐old) dogs were given a single dose of aspirin at 17.5 mg/kg body weight i.v. and a single dose of buffered aspirin at 35 mg/kg body weight p.o. Blood was collected from the jugular vein for 24 h following each dose. A fluorescence polarization immunoassay was used for determination of salicylate in plasma. Significant differences in aspirin disposition were identified between the two groups. Immature dogs had significantly shorter salicylate half‐life, lower mean residence time, and more rapid salicylate clearance than adult dogs. The difference in volume of distribution between the two groups was not significantly different. Immature dogs had lower mean (± SD) peak plasma salicylate concentrations (64.5 ± 2.38 mg/L) than adult dogs (95.9 ± 12.2 mg/L) following a single oral dose of buffered aspirin at 35 mg/kg body weight. Predicted plasma salicylate concentration‐time curves were constructed for various aspirin dosage regimens. This analysis showed that the previously recommended buffered aspirin dose for adult dogs of 25 mg/kg body weight p.o. every 8 h would be ineffective in maintaining plasma salicylate concentrations > 50 mg/L in immature dogs.
The disposition of suxibuzone in the horse
Authors: DELBEKE F. T. , VYNCKIER L. , DEBACKERE M.
Published: April 2008

A high performance liquid chromatographic method is described to determine the anti‐inflammatory drug suxibuzone (SXB) and its major metabolites phenylbutazone (PBZ) and oxyphenbutazone (OPBZ) in equine plasma and urine. When suxibuzone (6 mg/kg) was administered intravenously (i.v.) or orally (p.o.) no parent drug was detected in plasma or in urine. The disposition of the metabolite PBZ (i.v.) could be described by a 2 compartment model with a P half‐life varying from 7.40 to 8.35 h. Due to severe side effects the use of i.v. suxibuzone should not be encouraged in the horse. PBZ and OPBZ were detected in plasma and urine after p.o. SXB administration. Peak plasma PBZ concentrations (8.8 ± 3.0 μg/ml) occurred 6 h after oral dosing and the terminal exponential constant was 0.11 ± 0.01 h‐1. Phenylbutazone and oxyphenbutazone were detectable in urine (> 1 μg/ml) for at least 36 h, after p.o. administration.

SXB was not hydrolyzed in vitro by horse plasma. Equine liver homogenates however appeared to have a very high capacity for hydrolysing SXB, indicating that first‐pass effect could be responsible for the rapid disappearance of this NSAID in the horse.
Pharmacokinetics of diminazene in female Boran (Bos indicus) cattle
Authors: ALIU Y. O. , MAMMAN M. , PEREGRINE A. S.
Published: April 2008

The disposition kinetics and bioavailability of diminazene in five healthy heifers were determined after single intravenous (i.v.) and intramuscular (i.m.) administration of the drug in sequence with a wash‐out period between administrations of 6 weeks. Intact diminazene in plasma, whole blood and urine samples was analysed using high‐performance liquid chromatography. Nonlinear regression analysis of the i.v. and i.m. data indicated that, for either route, the plasma disappearance curves of diminazene were best described by triexponential equations. The i.v. bolus was followed by rapid and biphasic distribution with half‐life values of 0.04 h and 0.58 h, Vd(ss) was 1.91 ± 0.42 1/kg, elimination half‐life was 31.71 h while CI averaged 1.74 ± 0.40 ml/min/kg. Within 30 min of the i.v. dose, the erythrocyte/plasma partition ratio of diminazene was 0.30 ± 0.15. Diminazene was rapidly absorbed following i.m. administration; t½ka was 0.60 h. Cmax, 4.68 ± 1.12 μg/ml, was attained in 10–15 min and systemic availability was 102.42 ± 7.25%. The half‐life of the terminal disappearance phase was 145.48 h. About 8.26% of the i.m. dose was excreted intact in the urine within the first 24 h of treatment. In vitro, diminazene was bound to bovine plasma albumin to the extent of 38.01–91.10%.
Sulphadimidine metabolismin vitro:I. sex differences in acetylation and hydroxylation in cultured rat hepatocytes
Authors: KLOOSTER G. A. E. VAN T , NIJNANTEN F. M. A. WOUTERSEN‐VAN , BLAAUBOER B.J. , NOORDHOEK J. , MIERT A. S.J. P. A. M. VAN
Published: April 2008

The hydroxylation and acetylation of 0.5 mM sulphadimidine (SDD) was studied in primary cultures of hepatocytes from male and female rats, and from castrated male and sham operated male rats. In addition, SDD metabolism was investigated in hepatocytes from castrated male rats treated with testosterone, prior to liver cell isolation. In male rat hepatocytes a significantly higher hydroxylation activity was observed than in hepatocytes from female and castrated male rats. Acetylation activity was higher in females. Testosterone induced hydroxylation but did not affect acetylation. These results correlate well with data from previousin vivostudies, showing the relevance of thisin vitromodel.
Disposition, bioavailability and clinical efficacy of orally administered acepromazine in the horse
Authors: HASHEM A. , KELLER H.
Published: April 2008

The pharmacokinetics and pharmacological efficacy of orally (p.o.) administered acepromazine were studied and compared with the intravenous (i.v.) route of administration in a cross‐over study using six horses. The oral kinetics of acepromazine can be described by a two‐compartment open model with first‐order absorption. The drug was rapidly absorbed after p.o. administration with a half‐life of 0.84 h, tmax of 0.4 h and Cmax of 59 ng/ml. The elimination was slower after p.o. administration (half‐life 6.04 h) than after i.v. injection (half‐life 2.6 h). The bioavailability of the orally administered drug formulation was 55.1%. After p.o. administration of 0.5 mg/kg acepromazine, the parameters of the sedative effect were similar to those obtained after i.v. injection of 0.1 mg/kg. The effect of the drug on blood cell count and haemoglobin content was similar after both p.o. administration and injection, while the effects on the parameters of penile prolapse and on the mean arterial blood pressure were less pronounced after p.o. administration than after injection. After p.o. administration, no significant effects on haematoerit‐level as well as on the heart and respiratory rates were observed, while these parameters were significantly affected after injection. It is concluded that the high initial plasma level of the drug after i.v. injection may play a role in producing adverse effects of acepromazine.
Effect of endotoxin on tirilazad mesylate (U74006F) pharmacokinetic parameters in neonatal calves
Authors: ROSE M. L. , SEMRAD S. D. , PUTNAM M. L. , BROWN S. A.
Published: April 2008

Rose, M.L., Semrad, S.D., Putnam, M.L., Brown, S.A. Effect of endotoxin on tirilazad mesylate (U74006F) pharmacokinetic parameters in neonatal calves.J. vet. Pharmacol. Therap. 16, 438–445.

The pharmacokinetics of the 21‐aminosteroid tirilazad mesylate (U74006F) were studied in both healthy and endotoxin‐challenged neonatal calves. Group I calves received a 3‐h intravenous (i.v.) infusion of sterile saline (250 ml) and tirilazad mesylate (1.5 mg/kg i.v.) 1 h after the start of the saline infusion. Group II calves received tirilazad mesylate 1 h after the start of a 3‐h endotoxin (3.25 m̈g/kg) infusion. The data obtained indicate that tirilazad mesylate follows a biexponential equation in neonatal calves. The area‐derived volume of distribution (Vdarea) was 9.68 ± 0.759 1/kg in healthy calves and 6.53 ± 1.20 1/kg in endotoxin‐challenged calves (P< 0.05). Similarly, significant(P<0.05) decreases in steady‐state volume of distribution (Vjss) and central volume (VJ were observed in endotoxin‐challenged calves (5.32 ± 0.979 1/kg and 1.68 ± 0.189 1/kg, respectively) compared to healthy calves (7.58 ± 0.834 1/kg and 2.43 ± 0.452 1/kg, respectively). A and B were significantly larger in endotoxin‐challenged calves than in healthy calves (P< 0.05). Rate constants and their associated half‐lives, area under the curve and clearance were not significantly altered by endotoxin challenge. Serum thromboxane generation(ex vivo)was evaluated as a marker of the drug's physiologic activity. There was no significant difference in thromboxane generation during clotting of blood from healthy and endotoxemic calves treated with tirilazad mesylate.
Disturbances in ex vivo vascular smooth muscle responses following exposure to Pasteurella haemolytica vaccines
Authors: WEEKLEY L. B. , EYRE P.
Published: April 2008

Weekley, L.B., Eyre, P. Disturbances in ex vivo vascular smooth muscle responses following exposure to Pasturella haemolytica vaccines. J. vet. Pharmacol. Therap.16, 446–453.

Rats were vaccinated with saline (control) or one of the two commercially availablePasteurella haemolyticavaccines Presponse or Precon‐PH. Animals were killed 3 days later and thoracic aorta removed for evaluation of theex vivobiophysical responses to carbachol (CCh). In some experiments, vascular endothelium was mechanically removed. Vaccination of rats impairs the endothelial‐dependent relaxation to CCh. In vessels with endothelium removed, the contractile response to CCh is converted into a relaxation following vaccination. Treatment of endothelial‐denuded vascular ringsex vivowith methylene blue, a guanylate cyclase inhibitor, reduced the vaccination effect. Treatment of vascular rings with the superoxide dismutase inhibitor diethyl‐dithiocarbamate, impairs the relaxant reponse of de‐endothelialized vessels to CCh in Presponse vaccinated rats while enhancing the relaxation response of vessels from Precon‐PH vaccinated rats. De‐endothelialized vessels from vaccinated rats, but not control rats, relaxed in the presence of 7V‐monomethyl‐L‐arginine (L‐NMMA), a competitive inhibitor of nitric oxide synthetase. Furthermore, in the presence of L‐NMMA, the relaxant response to CCh is significantly enhanced by Precon‐PH but not Presponse. The normal relaxant response to hydrogen peroxide is converted into a contraction following vaccination. Results suggest that exposure to commercially availableP. haemolyticavaccines alters vascular smooth muscle reactivity to CCh and that several independent pathways may be altered.
Propofol as an induction agent in the goat: a pharmacokinetic study
Authors: REID J. , NOLAN A. M. , WELSH E.
Published: April 2008

Reid, J., Nolan, A.M., Welsh, E. Propofol as an induction agent in the goat: a pharmacokinetic study. J. vet. Pharmacol. Therap. 16, 488–493.

The pharmacokinetics of propofol, 4 mg/kg, administered as a bolus dose intravenously (i.v.) prior to the maintenance of anaesthesia with halothane in oxygen, were determined in five goats, and a clinical impression of its use as an induction agent was made. Induction of anaesthesia was rapid and smooth, providing satisfactory conditions for intubation in all animals. Post‐induction apnoea occurred in one goat and minimal regurgitation of ruminal contents was recorded in two animals. Recovery times were rapid with a mean time to standing after halothane inhalation ceased of 13.7 min. The blood propofol concentration time profile was best described by a bi‐exponential decline in all five goats. The mean elimination half‐life was short (15.5 min), the volume of distribution at steady state large (2,56 1/kg) and the clearance rapid (275 ml/min.kg). Propofol was shown to be a very satisfactory induction agent in the goat.
The acute haemodynamic effects of captopril in dogs with heart failure
Authors: KITTLESON M. D. , JOHNSON L. E. , PION P. D. , MEKHAMER Y. E.
Published: April 2008

The acute effects of three doses ofcaptopril(12.5, 25, and 50 mg [approximately 0.5, 1.O, arid 2.0 mg/kg]) on several haemodynamic variables and plasma aldosterone concentration were investigated in four dogs with experimentally produced heart failure (rapid ventricular pacing) and one dog with dilated cardiomyopattiy. Haemodynamic variables were measured with a Swan‐Ganz ttierniodilution catheter and an indwelling carotid artery catheter at baseline and 1, 2, and 4 h after drug administration. A statistically significant (P < 0.0.5) decrease in peripheral vascular resistance was observed 1 and 2 h following the 12.5 nig dose. A significant and large enough decrease in peripheral vascular resistance to produce a significant decrease in mean systemic arterial blood pressure was observed 1 and 2 ti after administering 25 and 50 mg of captopril.A mild but significant increase in cardiac output was observed 1 h after each dose. The drug effect on systemic arterial blood pressure lasted less than 4 h. No statistically significant changes were observed for the group in pulmonary capillary wedge pressure, right atrial blood pressure, or plasma aldosterone concentration at any time. We conclude that the acute haemodynamic benefits provided by captopril atlministration were mild and due primarily to arteriolar dilation. Doses of approximately 1–2 mg/kg produced slightly greater arteriolar dilation than an approximate dose of 0.5 mg/kg. The drug effect was short‐lived, lasting less than 4 h.
Lidocaine decay and hepatic extraction in the Pig
Authors: METS B. , ALLIN R. , DYKE J. VAN , HICKMAN R.
Published: April 2008

Plasma lidocaine decay after injection was studied in five anaesthetized pigs and fitted to a two compartment open model. Derived pharniacokinetic paranieter‐s were eniployed to rapidly achieve plateau concentrations within 60 min of starting a two stage infusion of lidocaine hydrochloride. Hepatic extraction and clearance of lidocaine at steady state were determined in 10 pigs by transhep;ttic: sampling and nieasurenient of hepatic arterial and portal venous blood flow using perivascular ultrasonic flow probes placed at laparotomy. These data were compared with siniilar studies performed in man as well as the sheep, (log, monkey and cat. The lidocaine extraction ratio of 0.60 in the pig was found t o be similar to that determined by others in man.
Pharmacokinetic disposition of intravenous and oral pentoxifylline in horses
Authors: CRISMAN M. V. , WILCKE J. R. , CORRELL L. S. , IRBY M. H.
Published: April 2008

The pharmacokinetics of pentoxifylline (P) and its alcohol metabolite I (MI) were determined after administration of intravenous pentoxifylline, sustained release pentoxifylline tablets (Trental®), and crushed pentoxifylline tablets in corn syrup, to five healthy adult horses. Pharmacokinetics were evaluated in a model‐independent manner. After intravenous administration, pentoxifylline was rapidly eliminated (mean residence time 1.09 f 0.67 h), had a large steady‐state volume of distribution (2.81 f 1.16 Vkg), and high clearance (3.06 51.05 I/kg/h). Oral absorption of pentoxifylline from both dose forms varied

considerably between individuals. Times to peak concentration ranged from 1–10 h for either dose form. There was no difference in relative bioavailability (Fâ'™)between whole (0.98 k 0.30) and crushed Trental® tablets. Ratios between areas under the curve (AUC) for pentoxifylline and MI were different following administration of oral versus intravenous doses. This finding suggests that route of administration may affect the metabolic profile of pentoxifylline. Given the extreme differences in absorption characteristics between indi‐viduals in this study, recommendations are not made as to appropriate dose, dose interval, or dose form for administration of pentoxifylline to horses.
Hormonal regulation of oxidative drug metabolism in the dwarf goat. The effect of sex and hormonal treatment on plasma disposition and metabolite formation of sulphadimidine
Authors: WITKAMP R. F. , VAN' T KLOOSTER G. A. E. , NIJMEIJER S. M. , KOLKER H. J. , NOORDHOEK J. , MIERT A. S. J. P. A. M. VAN
Published: April 2008

Sulphadimidine (20 mg/kg i.v.) plasma elimination and metabolite formation were studied in intact male, castrated male, and female dwarf goats. Plasma pharmacokinetics and urinary metabolite patterns were first studied in un‐treated animals. Afterwards, females and castrates were treated with a combination of testosterone‐propionate (1 mg/kg) and 17P‐oestradiolbenzoate(0.02 mg/kg) once every 3 days, for a period of 4 weeks. In untreated animals, males showed a considerably lower plasma clearance than females or castrates. This was accompanied by lower partial clearances for the production of two hydroxylated sulphadimidine metabolites. After hormonal treatment of females and castrates, sulphadimidine plasma clearance was significantly reduced, to values corresponding with those observed in control males. Furthermore, hydroxylation was significantly inhibited after treatment. The results indicate that sulphadimidine hydroxylation in the goat is performed by enzymes of the cytochrome P450 complex which are strongly influenced by gonadal hormones. Androgens seem to play a central role in this respect.
Plasma ronidazole concentrations in sheep after intravenous, oral, intraruminal and intraabomasal administration
Authors: VYNCKIER L. J. , DEBACKERE M.
Published: April 2008

Plasnia ronidazole concentrations were examined after intravenous (i.v.) antloral administration of ronidazole in sheep (t i = 6) at;I dosage of 5 mg/kg Iiody weight. In three sheep a ruminal and an abomasal fistula were inserted. l'heronidazole determinations were performed by an HPLC method. Oral bioav;iil‐ability in the fistulated sheep was only 5.5 k 1.8% (mean k SE). Somewhat lower values (4.6 k 1.45%) were obtained when the drug was administered through the ruminal fistula in the rumen. After administration of the sanie dose directly in the abomasum through the intraaboiiiasal fistula, 1)ioavailability was increased t o 86.0 k 8.9%. In the non‐fistulated sheep, oral biodisponibility was 2.6 k 0.5%.

After water was restricted for 48 h before the oral ronidazole administration t o

these sheep, bioavailability was slightly increased (6.0 k 9.1 %). When desmo‐

pressin acetate was injected i.v. before the oral ronidazole;idministration,

bioavailability was 10.6 k 6.5%. When glypressiii,;t1101her vasopressin analogue,

was used, oral bioavailability was not influenced: 2.4 f 1.3%. Konitlazole was

also incubated with ruminal contents antl the ronitlamle concer1tr;ition tle‐

creased with a first order rate constant of ‘0.122 rfr 0.050 miri‐’ (mean f SF,).

These results suggest that oral atfrniiiistration of ronidazole to sheep is o f little

therapeutic use, because most is metabolised by the ruminal triicro‐organisiiis

before it can reach the circulation. A second conclusion we can make is that i t is

very difficult, if not impossible, at least with the methods used, to influence

gastro‐intestinal motility in sheep to get a reprotlucahle closure of I he

oesophageal groove.
Bioavailability and pharmacokinetics of metoclopramide in cattle
Authors: JONES R. D. , MIZINGA K. M. , THOMPSON F. N. , STUEDEMANN J. A. , BOWEN J. M.
Published: April 2008

The bioavailability of metoclopramide was investigated in three steers following administration of 8 mg/kg by the oral, abomasal (cannula), and intravenous routes, using a Latin square design. The mean (± SD) oral and abomasal bioavailabilitles were 51.3 ± 30.7% and 76.2 ± 15.5%, respectively. The mean value for clearance (C1) was 20.1 ± 5.9 ml/min and the volume of distribution (Vd) was 0.51 ± 0.19 1/kg. Additionalpharmacokmetic parameters for metoclopramide were determined following intravenous administration to seven cows. A predominate two‐compartment model of distribution was found in six cows with a t1/2α harmonic mean of 24.2 min and a range of 11.2–72.4 min, a t1/2β harmonic mean of 53.1 min and a range of 31.1–134.1 min, a Cl of 42.2 ± 8.7 ml/min, and a Vd of 2.1 ± 0.8 1/kg. To better define the relationship between metoclopramide concentration and release of prolactin, a treatment‐by‐subjects infusion study was conducted in which four different loading doses followed by constant infusion were used. A steady‐state metoclopramide concentration (MCPss) of 8.8 ± 2.6 ng/ml was associated with a three‐fold elevation of prolactin to a mean value of 12.1 ± 3.1 ng/ml in six yearling steers. Steady state serum prolactin concentrations (PRLss) did not rise significantly above 23.3 ± 6.9 ng/ml, even when MCPss reached a concentration of 518.5 ±151.2 ng/ml. The short half‐life, moderate Vd, low minimum pharmacologically effective concentration, and rapid C1 found for metoclopramide in cattle in this study, suggest that a continuous release device could potentially be useful in the application of this drug in the prevention and treatment of fescue toxicosis.
Pharmacokinetics of florfenicol following intravenous and intramuscular doses to cattle
Authors: LOBELL R. D. , VARMA K. J. , JOHNSON J C , Sams R. A. , GERKEN D. F. , ASHCRAFT S. M.
Published: April 2008

The disposition of florfenicol after single intravenous and intramuscular doses of 20 mg of florfenicol/kg of body weight (b.w.) to feeder calves was investigated. Serum florfenicol concentrations were determined by a sensitive high performance liquid chromatographic method with a limit of quantitation of 0.025 μg/ml. The extent of serum protein binding of florfenicol was only 13.2% at a serum florfenicol concentration of 3.0 μg/ml. Serum concentration‐time data after intravenous administration were best described by a triexponential equation. Total body clearance and steady state volume of distribution were 3.75 ml/min/kg b.w. and 761 ml/kg b.w., respectively. The terminal half‐life after intravenous administration was 159 min. The absolute systemic availability after intramuscular administration was 78.5% (range: 59.3–106%) and the harmonic mean of the terminal half‐life was 1098 minutes, indicating slow release of the florfenicol from the formulation at the intramuscular injection site.
Comparative study of the action of flunixin meglumine and tolfenamic acid on prostaglandin E2 synthesis in bovine inflammatory exudate
Authors: ESPINASSE J. , THOUVENOT J. P. , DALLE S. , GARCIA J. , SCHELCHER F. , SALAT O. , VALARCHER J. F. , DAVAL S.
Published: April 2008

An acute non‐immune inflammation model was used to compare the action of two non‐steroidal anti‐inflammatory drugs, flunixin meglumine and tolfenamic acid, on prostaglandin E2, (PGE2) synthesis in bovine inflammatory exudate. The tissue cage model used involves subcutaneous implantation of polypropylene cages and subsequent stimulation by carrageenan injection of the granulation tissue which develops within the cage. Twelve calves were randomly assigned to three groups receiving placebo, flunixin meglumine and tolfenamic acid, respectively. Inflammatory exudate was sampled 30 min after carrageenan injection and at seven subsequent time points. PGE2, levels were determined by radioimmunoassay. At each time point post‐carrageenan injection, flunixin meglumine inhibited PGE2, synthesis to a greater extent than tolfenamic acid. At 4, 8,12 and 24 h these differences were statistically significant.
Effect of drug formulation and feeding on the pharmacokinetics of orally administered quinidine in the horse
Authors: BOUCKAERT S. , VOORSPOELS J. , VANDENBOSSCHE G. , DEPREZ P. , REMON J. P.
Published: April 2008

Quinidine is the drug of choice for the treatment of cardiac arrhythmias in horses. The plasma concentrations vs. time profiles following oral administration of two formulations of quinidine sulphate, an oral solution and an oral suspension paste, were evaluated in nine horses. They received multiple administrations of the oral solution under fed and non‐fed conditions and of the paste under non‐fed conditions. A loading dose of 20 mg.kg‐1 and a maintenance dose of 10 mg.kg‐1 quinidine with dosing interval of 6 h were used. The relative bioavailability of the oral solution under fed conditions in comparison to the solution under non‐fed conditions was 75.0 ± 10.2% for the loading dose and 97.18 ± 31.66% after the fourth dose. For the paste formulation the relative bioavailability values are not reported, as steady‐state levels were not reached. There was a large variation in plasma quinidine levels when the paste formulation was administered. Feeding conditions had a significant influence on the Cmax, values after administration of the loading dose. The Tmax values were not affected by food intake. It was concluded that an oral solution has to be preferred because of the variable drug bioavailability from the paste formulation and the poor acceptability of the paste by the horse.
A comparison of the effects of buprenorphine, carprofen and flunixin following laparotomy in rats
Authors: LILES J. H. , FLECKNELL P. A.
Published: April 2008

Rats underwent a midline laparotomy and received buprenorphine, buprenorphine together with carprofen, flunixin or carprofen alone while a control group received saline. Food and water intakes and body weight were reduced following surgery in the saline control group. The degree of depression of these variables was significantly reduced by the administration of either buprenorphine or carprofen. In all groups of rats locomotor activity was depressed following surgery. Analgesic administration had little influence on these changes in activity, although administration of two doses of buprenorphine (0.05 mg/kg, 9 h interval) reduced the degree of depression in comparison to the saline control group. If the depression in food and water consumption is related to the presence of post‐operative pain, then these findings suggest that analgesics should be administered to rats following surgical procedures.
Plasma disposition of amikacin and interactions with gastrointestinal microflora in Equidae following intravenous and oral administration
Authors: HORSPOOLs L. J. I. , TAYLOR D T. , McKELLAR Q A
Published: April 2008

Amikacin was detectable (> 0.02 μg/ml) in plasma for 12 h in horses and donkeys and for 8 h in ponies following intravenous (i.v.) administration at a dose the rate of 6 mg/kg bodyweight The elimination half‐life (harmonic mean) of amikacin was 2.8, 1.6 and 1.9 h in horses, ponies and donkeys, respectively, and the mean body clearance was relatively slow (45.2, 82.4 and 58.0 ml/h.kg, respectively). A suitable dosage interval for the i.v. administration of amikacin sulphate to horses, ponies and donkeys, at a dose rate of 6 mg/kg, would be every 8 h in horses, and every 6 h in ponies and donkeys. Following i.v. administration there were no marked alterations in caecal liquor pH, the number of viable bacteria isolated, or the short chain fatty acid (SCFA) concentrations in caecal liquor and faeces. Amikacin was not detected (< 0.02 μg/ml) in plasma following administration by nasogastric tube to ponies with cannu‐lated caecal fistulae; however, there were high concentrations of amikacin measured in caecal liquor (maximum 16.2–99.4 μg/ml). Despite the high drug concentrations in caecal liquor, there were only slight alterations in the number of viable bacteria isolated. However, there was a reduction in caecal liquor pH to < 6.6, but few changes in caecal liquor SCFA concentrations. Faecal SCFA concentrations, dry matter content and consistency did not alter markedly.
Disposition of human drug preparations in the horse. III. Orally administered alclofenac
Authors: DELBEKE F. T. , LANDUYT J. , DEBACKERE M.
Published: April 2008

Concentrations of the non‐steroidal anti‐inflammatory drug (NSAID) alclofenac were determined by a sensitive high performance liquid chromatographic procedure in plasma and urine of horses following oral administration of a dose of 3 g. In plasma, alclofenac was present in detectable concentrations for 72 h. The plasma disposition in individual horses was best described by a bi‐compartmental model with two successive rate constants ka1= 0.05 ± 0.06 h‐1 and ka2= 0.06 ± 0.01 h‐l. Alclofenac half‐lives t½ and t1/2β were 1.0 ± 0.8 h and 6.9 ± 1.5 h, respectively. Maximal concentrations (38.9 ± 16.2 μg/ml) were obtained after 8.5 ± 2.4 h. Alclofenac was detected in urine for at least 48 h after dosing. The percentage of the dose excreted as unchanged alclofenac in 12 h was very low (0.68 ± 0.19%), total (free + conjugated) alclofenac accounted for 2.16 ± 0.55% of the dose.