Swan G E, Guthrie A J, Mülders M S, Killeen V M, Nurton J P, Short C R, van den Berg J S
Department of Pharmacology and Toxicology, Faculty of Veterinary Science, University of Pretoria, Onderstepoort, Republic of South Africa.
J S Afr Vet Assoc. 1995 Sep;66(3):151-6.
The pharmacokinetics of gentamicin following single and multiple intravenous and intramuscular doses were compared in a two phase, randomised cross-over study in horses. Gentamicin was administered to 6 healthy, conditioned Thoroughbred mares at a dosage of 3.3 mg/kg body weight every 12 hours for 5 intravenous or intramuscular consecutive treatments. Equal numbers of horses were treated by either route during each phase. There was a wash-out period of 5 days between phases. During each phase serial blood samples were collected from each mare immediately before treatment and at 16 intervals following the first and fifth administrations. Blood samples were also collected immediately before treatment and at 30 and 60 minutes following doses 2 through to 4. Gentamicin plasma concentrations were determined by fluorescence polarisation immunoassay. Plasma gentamicin concentration versus time data for both single and multiple doses by either route was best described by a 2 compartmental open model with first order rate constants. A distribution half-life (T1/2 alpha) of 0.1 +/- 0.1 hours, terminal half-life (T1/2 beta) of 1.2 +/- 0.2 hours, mean residence time (MRT) of 1.4 +/- 0.1 hours and total body clearance (ClB) of 1.4 +/- 0.2 ml/kg/min were observed following multidose gentamicin intravenous administration. The volume of distribution at steady state (Vdss) was 117.6 +/- 10.8 ml/kg. No significant differences (P > 0.05) were observed for any of the parameters between single or multiple doses for either route of administration. Except for AUC, significant (P < or = 0.05) differences were observed between multiple intravenous and intramuscular treatments for all pharmacokinetic parameters determined.(ABSTRACT TRUNCATED AT 250 WORDS)
在一项针对马匹的两阶段随机交叉研究中,比较了庆大霉素单次及多次静脉注射和肌肉注射后的药代动力学。对6匹健康、经训练的纯种母马每12小时给予3.3毫克/千克体重的庆大霉素,连续进行5次静脉或肌肉注射治疗。每个阶段通过两种途径治疗的马匹数量相等。阶段之间有5天的洗脱期。在每个阶段,在每次治疗前以及首次和第五次给药后的16个时间点,从每匹母马采集系列血样。在第2至4次给药前及给药后30分钟和60分钟也采集血样。通过荧光偏振免疫测定法测定庆大霉素血浆浓度。单次和多次给药后,两种途径的血浆庆大霉素浓度与时间数据均以具有一级速率常数的二室开放模型最佳描述。多次静脉注射庆大霉素后,观察到分布半衰期(T1/2α)为0.1±0.1小时,末端半衰期(T1/2β)为1.2±0.2小时,平均驻留时间(MRT)为1.4±0.1小时,全身清除率(ClB)为1.4±0.2毫升/千克/分钟。稳态分布容积(Vdss)为117.6±10.8毫升/千克。两种给药途径的单次或多次给药之间,任何参数均未观察到显著差异(P>0.05)。除AUC外,多次静脉注射和肌肉注射治疗之间,所有测定的药代动力学参数均观察到显著(P≤0.05)差异。(摘要截短至250字)