摘要:

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 withTrichostrongylus colubriformisandHaemonchus 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

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00171.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The pharmacokinetic disposition of closantel was examined following intraruminal (i.r.) or intramuscular (i.m.) administration to adult Merino sheep and to adult and 3‐month‐old, suckling Angora goats. In adult goats the maximum concentration (Cmax) and area under the plasma concentration with time curve (AUC) following 3.75, 7.5 and 15.0 mg closantel/kg given i.r. increased with dose however the time of Cmax(rmax= 2.6d) in plasma was unaffected by dose rate. The elimination phase (K10) of closantel was monoexponential with a half‐life (t½) of 4.7d again unaffected by dose rate. Apart from a more rapid absorption phase and earlier Tmaxfollowing 3.75 mg closantel/kg i.m., pharmacokinetic behaviour was similar to that following i.r. administration at 3.75 or 7.5 mg/kg. Although absorption rate was more rapid in kids after i.r. administration at 7.5 mg/kg, pharmacokinetic disposition of closantel was otherwise similar to that in adult goats. No closantel was detected in milk of treated does or in the plasma of their kids. I.R. closantel at 7.5 mg/kg was more slowly absorbed in goats than in sheep but Cmaxwas similar in both species. However, K10t½was significantly shorter in goats (4d) than in sheep (14d). Faster elimination resulted in an almost three‐fold lowering ofAUCin goats and could dramatically reduce the sustained action of closantel in this species compared w

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00172.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Plasma concentrations of febantel and its major metabolites fenbendazole, oxfendazole and oxfendazole sulphone were determined after oral administration of 7.5 mg/kg febantel in lambs before and 28 days after infection with 50 000 L3larvae ofOstertagia circumcinctaorTrichostrongylus colubriformis.The febantel concentrations were always very low and only in a few samples higher than the detection limit. The mean decrease inAUCfor the three metabolites for the infected sheep in comparison to the parasite naive sheep was 13.9%± 4.1% (mean± SEM) and 23.7%± 5.3% in the0. circumcinctainfected and theT. colubriformisinfected lambs respectively. This reduction was only significant for theT. colubriformisinfected group.In order to determine a more complete pharmacokinetic profile, febantel was injected intravenously at a dose of 2.5 mg/kg in a further stu

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00173.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 m

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00174.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 hydrolyzedin vitroby 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 i

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00175.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

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 whileCIaveraged 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;t½kawas 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 exte

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00176.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

Ribavirin, a broad‐spectrum antiviral agent activein vitroagainst a number of RNA and DNA viruses, has been associated with moderate toxicity in laboratory animals and humans. Clinically, ribavirin has been used effectively in persons primarily to treat life‐threatening viral diseases such as acute haemorrhagic fever or viral pneumonia of infants. In order to evaluate the feasibility of using this antiviral agent in cats, the effects of oral (p.o.), intramuscular (i.m.) and intravenous (i.v.) doses of ribavirin in 27 9‐month‐old specific‐pathogen‐free cats were evaluated by haematology, clinical chemistries, bone marrow biopsies and histopathology. Ribavirin was administered once daily for 10 consecutive days at a dose of either 11, 22, or 44 mg/kg after which all cats were euthanatized and necropsied. Most cats receiving 22 or 44 mg of ribavirin/kg became anorectic and suffered some degree of weight loss (0.2 to 0.6 kg), and about one‐third of the cats developed diarrhoea and/or mucous membrane pallor. Icterus or haemorrhage was not observed. The most profound and consistent haemato‐logic change, particularly among the moderate and high dosage groups regardless of route of administration, was a significant and severe thrombocytopenia (range, 33–78% reduction in mean platelet counts vs. baseline). Other changes, particularly reductions in total WBC and neutrophils and reductions in RBC and PCV, tended to occur at lower ribavirin dosages, but generally they were not statistically significant. Cats given 44 mg of ribavirin/kg i.v. showed significant decreases in leukocyte variables, including total WBC (P = 0.016), neutrophils (P= 0.026) and lymphocytes (P= 0.047). Mild‐to‐moderate increases in serum alanine aminotransferase and alkaline phosphatase activities occurred at doses of 22 and 44 mg/kg. Evaluation of bone marrow biopsies before and after treatment revealed that cats given 11 mg of ribavirin/kg had mild megakaryocytic (MK) hypoplasia, whereas cats receiving 22 or 44 mg/kg had progressively severe degrees of MK hypoplasia and dysplasia, asynchronous MK maturation, and increased myeloidrerythroid ratio. Pathologic changes in ribavirin‐treated cats generally were mild and included primarily enteritis (seven cats) and hepatocellular vacuolation and/or centrilobular necrosis (seven cats). Results of this study in cats indicated that daily administration of ribavirin at a dose range of 11 to 44 mg/kg induced a dose‐related toxic effect on bone marrow, primarily on megakaryocytes and erythroid precursors, and at the higher dosages it suppressed numbers

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00177.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The disposition of an aqueous suspension of procaine penicillin G (300 000 U/ mL) was studied in feedlot steers. Four groups of three steers were used. Steers in groups 1 and 2 received procaine penicillin G once daily for 5 days intramuscularly (i.m.) at a dose of 24 000 U/kg (group 1) or of 66 000 U/kg (group 2). The injection on the last day was administered in the gluteal muscle. Steers in group 3 (i.m. neck injection) and group 4 [subcutaneous (s.c.) injection] each received a single dose of procaine penicillin G at a dose of 66 000 U/kg.From every animal, after the last injection in groups 1 and 2 and following the single injection in groups 3 and 4, a series of blood samples was taken at fixed time intervals. The plasma from these samples was analysed for penicillin G by a high performance liquid chromatography (HPLC) assay in order to determine the disposition of penicillin.The maximum plasma concentration (Cmax) and the area under the curve (AUC) were significantly different between groups 1 and 2, but we found no difference in the disappearance rate constant between these two groups. Group 4 single s.c. injections produced a lower mean Cmax(1.85 ± 0.27 ng/mL) than the mean Cmax(4.24 ± 1.08 μg/mL) produced in group 3 by i.m. injections into the neck muscle or the mean Cmax(2.63 ± 0.27 μg/mL) produced in group 2 by i.m. injections into the gluteal muscle. However the mean Cmaxproduced by i.m. injections into the neck muscles (group 3) was higher than the mean Cmaxproduced by i.m. injections into the gluteal muscle (group 2). Additionally, the disappearance t½, was longer (18.08 h) in group 4 following the s.c. injection and shorter (8.85 h) in group 3 following the i.m. neck injection, than thet½following administration of the same dose i.m. into the gluteal muscle (15.96 h) in group 2. In this study, when procaine penicillin G was injected into the gluteal muscle, doses of 66 000 U/kg were necessary to produce plasma concentrations that were above a minimum inhibitory concentration(MIC)for penicillin G of 1.0 μg/mL as compared to doses of 24 0

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00178.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The effects of a 3‐day intramuscular (i.m.) administration of clenbuterol (25 μ.g/ Kg), propranolol (12 mg/kg), clenbuterol (25 μg/kg) plus propranolol (12 mg/ Kg) and estradiol (0.5 μg) upon the female reproductive system were investigated in immature Sprague‐Dawley rats. Clenbuterol and estradiol treatments induced a significant increase in uterus weight and in relative uterus weight, whereas in the groups treated with propranolol and clenbuterol plus propranolol no differences were detected versus controls. The uterine estrogen receptor levels were significantly increased by clenbuterol administration. In the rats dosed with propranolol and clenbuterol plus propranolol, no modifications occurred in estrogen receptor concentrations when compared with control values. Uterine progesterone receptors were never significantly affected by any of the considered treatments. Data obtained indicate that clenbuterol treatment induces an increase in uterus weight and in estrogen receptor levels and that these effects are regulated by acute beta‐adrenergic stimulation, as the contemporaneous administration of high doses of a beta‐blocker inhibit su

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00179.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY

摘要:

The pharmacokinetics of propofol, 6.5 mg/kg, administered as a bolus dose intravenously (i.v.) were studied in six dogs (group 1). The effect of maintaining anaesthesia with halothane and nitrous oxide in oxygen on propofol pharmacokinetics was also investigated in six dogs undergoing routine anaesthesia (group 2). Induction of anaesthesia was rapid in all animals. Post‐induction apnoea was a feature in three of the 12 dogs. The blood propofol concentration‐time profile was best described by a bi‐exponential decline in two dogs in group 1 and in 3 dogs in group 2, and by a tri‐exponential decline in four dogs in group 1 and 3 dogs in group 2. The elimination half‐life was long in both groups (90.9 min and 75.2 min, respectively), the volume of distribution at steady state large (4889 and 4863 ml/kg) and the clearance rapid (58.6 and 56.3 ml/kg.min). There were no significant differences between the groups, thus indicating that maintenance of anaesthesia with halothane and nitrous oxide had no effect on the pharmacokinetics of propofol i

ISSN:0140-7783    

DOI:10.1111/j.1365-2885.1993.tb00180.x

出版商:Blackwell Publishing Ltd    

年代:1993

数据来源: WILEY