ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00758.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00759.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

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, Athe

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00760.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Waterman, A.E.&Kalthum, W. The effect of clinical hepatic disease on the distribution and elimination of pethidine administered post‐operatively to dogs.J. vet. Pharmacol. Therap.13, 137–147.The pharmacokinetics of pethidine were investigated in dogs suffering from portosystemic vascular shunts and hepatic parenchymal disease. The drug was administered post‐operatively at a dose rate of 2.0 mg/kg either intravenously or intramuscularly. When the drug was given intravenously to dogs suffering from intrahepatic shunts, the elimination half life was 75.5 ± 4.2 min and the clearance rate was 29.0 ± 2.3 ml/kg min. When the drug was given intramuscularly its rate of absorption was very slow (57.9 ± 6.1 min) and the time taken to reach the maximum plasma concentration was long at 26.7 ± 6.4 min. The elimination half‐life for the intramuscularly administered drug was also very slow at 108.0 ± 13 min, reflecting the reduced ability of these dogs to metabolize and eliminate pethidine. These findings suggest that caution should be exercised in the administration of pethidine to dogs suffering from hepatic dysfunction. In particular, the slower rate of absorption should be remembered in judging whether or not maximum effects have been achieved and the longer elimination half‐life indicates the need to extend the intervals between repeat doses of this analgesic.A. E. Waterman, Department of Veterinary Surgery, University of Bristol, Langford House, Langford, Bristo

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00761.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Nap, R.C., Breen, D.J., Lam, T.J.G.M.&de Bruyne, J.J. Gastric retention of enteric‐coated aspirin tablets in beagle dogs.J. vet. Pharmacol. Therap.13, 148–153.Administration of acetylsalicyclic acid (ASA) in the dog may cause gastric mucosal damage. Enteric‐coated tablets protect the canine stomach during oral ASA medication. A therapeutic plasma salicylate concentration can be attained using enteric‐coated ASA tablets at a dose rate of 25 mg/kg body wt, administered every 8 h. Six beagle dogs were given enteric‐coated ASA tablets (500 mg) orally, in a 5‐day cross‐over experiment on two different feeding regimens: i.e. feeding once daily (Group I) or 8 hourly (Group II). Results demonstrate that feeding regimen strongly influences the plasma salicylate concentration pattern. Subtherapeutic mean plasma salicylate concentrations were found in both groups. In Group II the standard deviation (SD) of the mean plasma salicylate concentration was larger than that of Group I. The minimal plasma salicylate concentration never reached detectable levels in Group II. In both groups large numbers of tablets were vomited. Gastric evacuation of the ASA tablets is comparable to indigestible solid particles; their removal was dependent on the interdigestive gastric motility. It is concluded that large enteric‐coated ASA tablets are not suitable for therapeutic use in small dogs.R. C. Nap, Department of Clinical Sciences of Companion Animals, Uirechl University, PO Box 80. 154, 3508 TD, Utrecht,

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00762.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Scherkl, R., Hashem, A.&Frey, H.‐H. Apomorphine‐induced emesis in the dog‐routes of administration, efficacy and synergism by naloxone.J. vet. Pharmacol. Therap.13, 154–158.Apomorphine proved to be more effective as an emetic in dogs after s.c. administration than after i.m. injection with doses of 0.04 and 0.1 mg/kg. This effect is explained by an anti‐emetic effect mediated by μ‐receptors in the vomiting centre in die brain, which, in contrast to the chemoreceptor trigger zone, is within the blood‐brain barrier. A certain delay between the stimulation of D2‐receptors in the chemoreceptor trigger zone (causing emesis) and μ‐receptors in the vomiting centre (producing anti‐emesis) therefore results, leading to a self‐limiting emesis. Blockade of the μ‐receptors by naloxone increased and prolonged the effect of apomorphine. A relatively narrow range of apomorphine concentrations on s.c. administration is then effective to stimulate the chemoreceptor trigger zone, but can hardly inhibit the vomiting centre, and must therefore be considered the most suitable route for administration of apomorphine.R. Scherkl, Department of Pharmacology and Toxicology, School of Veterinary Medicine, Free University of Berlin, Koserstr. 20

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00763.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Mevius, D.J., Breukink, H.J., Guelen, P.J.M., Jansen, T.&de Grève, B. Pharmacokinetics, metabolism and renal clearance of flumequine in veal calves.J. vet. Pharmacol. Therap.13, 159–169.The pharmacokinetics of flumequine was studied in 1‐, 5‐and 18‐week‐old veal calves. A two‐compartment model was used to fit the plasma concentration‐time curve of flumequine after the intravenous injection of 10 mg/kg of a 10% solution. The elimination half‐life (t1/2 ß) of the drug ranged from 6 to 7 h. The Vd ßand ClBof 1‐week‐old calves (1.07 1/kg, 1.78 ml/min/kg) were significantly lower than those of 5‐week‐old (1.89 1/kg, 3.23 ml/min/kg) and 18‐week‐old calves (1.57 1/kg, 3.10 ml/min/kg). After the oral administration of 10 mg/kg of a 2% flumequine formulation mixed with milk replacer, the Cmaxwas highest in 1‐week‐old (9.27 μg/ml) and lowest in 18‐week‐old calves (4.47 μg/ml). The absorption was rapid (Tmaxof approximately 3 h) and complete. When flumequine itself and a formulation containing 2% flumequine and 20 times 106iu of colistin sulphate were mixed with milk replacer and administered at the same dose rate, absorption was incomplete and Cmaxwas lower. The main urinary metabolite of flumequine was the glucuronide conjugate (approximately 40% recovery within 48 h of intravenous injection) and the second most important metabolite was 7‐hydroxy‐flumequine (approximately 3% recovery within 12 h of intravenous injection). Only 3.2–6.5% was excreted in the urine unchanged. After oral administration a ‘first‐pass’ effect was observed, with a significant increase in the excretion of conjugated drug. For 1‐week‐old calves it is recommended that the 2% formulation should be administered at a dose rate of 8 mg/kg every 24 h or 4 mg/kg every 12 h; for calves over 6 weeks old, the dose should be increased to 15 mg/kg every 24 h or 7.5 mg/kg every 12 h. The formulation containing colistin sulphate should be administered to 1‐week‐old calves at a flumequine dose of 12 mg/kg every 24 h or 6 mg/kg every 12 h.Dr D. J. Mevius, Department of Large Animal Medicine

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00764.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Lanusse, C.E.&Prichard, R.K. Pharmacokinetic behaviour of netobimin and its metabolites in sheep.J, vet. Pliarmacol. Therap.13, 170–178.The pharmacokinetics and the profile of urine excretion of netobimin (NTB) and its metabolites were investigated after its intraruminal (i.r.) and subcutaneous (s.c.) administration to sheep at 20 mg/kg. Plasma and urine concentrations of NTB, albendazole (ABZ), albendazole sulphoxide (ABZSO) and albendazole sulphone (ABZSO2) were measured serially over a 120‐h period by HPLC. NTB showed a similar pharmacokinetic profile in both treatments, being detected between 0.5 and 12 h post‐treatment, but the tmaxwas achieved significantly earlier (P<0.05) after s.c. treatment. ABZ was detected in plasma only after i.r. treatment, resulting in a low area under the curve (AUC).The peak plasma concentration (Cmax) andAUCfor ABZSO and ABZSO2were significantly higher after i.r. administration of NTB. In both treatments, the ABZSO Cmaxwas reached earlier than the ABZSO2Cmax. The ratio ofAUCABZSO2:ABZSO was higher following s.c. administration (1.33) than following i.r. administration (0.35). The percentages of total dose excreted in the urine as NTB, ABZ, ABZSO and ABZSO2, were 17.05 (i.r.) and 8.16 (s.c). There was a less efficient conversion of NTB into ABZ metabolites after s.c. administration. The detection of ABZ in plasma and the high ABZSOAUCobtained after i.r. treatment may be of major importance for anthelmintic efficacy.C. E. Lanusse, Institute of Parasitology, McGill University, Macdonald College, 21 III Lakeshore Road, Ste‐Anne de Bellevue, Quebec, Canada

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00765.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Firth, E.C., Nouws, J.F.M., Klein, W.R.&Driessens, F. The effect of phenylbutazone on the plasma disposition of penicillin G in the horse.J. vet. Pharmacol. Therap.13, 179–185.A pilot study in two ponies showed that the plasma concentrations of intramuscularly administered procaine penicillin were higher if phenylbutazone was administered concurrently. In two other trials, each involving five horses, intravenous sodium penicillin was administered with and without concurrent intravenously injected phenylbutazone, and procaine penicillin was injected intramuscularly with and without oral phenylbutazone. In both cases the plasma concentrations of penicillin were higher when phenylbutazone was given. The pharmacokinetic parameters indicated that the effect was probably due to a lower peripheral distribution because the penetration of penicillin into the tissues was greatly reduced.E. C. Firth, Veterinary Surgery and Companion Animal Health, Department of Clinical Sciences, Faculty of Veterinary Science, Massey University, Palmerston North, New Zealan

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00766.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Strøm, H.&Krogsgaard Thomsen, M. Effects of non‐steroidal anti‐inflammatory drugs on canine neutrophil chemotaxis.J. vet. Pharmacol. Therap.13, 186–191.Non‐steroidal anti‐inflammatory drugs exhibit differences in their ability to suppress polymorphonuclear leucocyte (PMN) functions in different species. The present study investigated thein‐vitroandex‐vivoeffects of phenylbutazone and flunixin on leukotriene‐B4‐directed migration of canine PMN. Furthermore,in‐vitrocomparison was made to indomethacin and the 5‐lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA).In vitro, flunixin and NDGA were the most potent inhibitors, withIC50s of 13 and 7 μmol/l, respectively. Phenylbutazone had anIC50of 42 μmol/l whereas indomethacin did not achieve 50% inhibition at concentrations less than 100 μmol/l.Ex vivo, flunixin almost completely abolished the LTB4response at 1h, and still possessed significant inhibitory activity 24 h after a dosage of 1mg/kg i.v. Phenylbutazone was less activeex vivobut did suppress chemotaxis by 23% (P<0.05) at 1h following an i.v. dose of 20mg/kg. It is suggested that part of the anti‐inflammatory action of flunixin in dogs may be attributed to inhibition of PMN recruitment.M. Krogsgaard Thomsen, Department of Pharmacology, Leo Pharmaceutical Products,

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1990.tb00767.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY