Duffee N E, Stang B E, Schaeffer D J
Division of Comparative Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
J Vet Pharmacol Ther. 1997 Dec;20(6):427-33. doi: 10.1046/j.1365-2885.1997.00085.x.
To evaluate the effect of foal age on the pharmacokinetics of cefadroxil, five foals were administered cefadroxil in a single intravenous dose (5 mg/kg) and a single oral dose (10 or 20 mg/kg) at ages of 0.5, 1, 2, 3 and 5 months. Pharmacokinetic parameters of terminal elimination rate constant (beta(po)), oral mean residence time (MRTpo), mean absorption time (MAT), rate constant for oral absorption (Ka), bioavailability F, peak serum concentrations (Cmax) and time of peak concentration (tmax), were evaluated in a repeated measures analysis over dose. Across animal ages, parameters for the intravenous dose did not change significantly over animal age (P > or = 0.05). Mean values +/- SEM were: beta(IV) = 0.633 +/- 0.038 h-1; Cl = 0.316 +/- 0.010 L/kg/h; Vc = 0.196 +/- 0.008 L/kg; Varea = 0.526 +/- 0.024 L/kg; VSS = 0.374 +/- 0.014 L/kg; MRTiv = 1.22 +/- 0.07 h; Kel = 1.67 +/- 0.08 h-1. Following oral administration, drug absorption became faster with age (P < 0.05), as reflected by MRTpo, MAT, Ka and tmax. However, oral bioavailability (+/- SE) declined significantly (P < 0.05) from 99.6 +/- 3.69% at 0.5 months to 14.5 +/- 1.40% at 5 months of age. To evaluate a dose effect on the pharmacokinetic parameters, a series of oral doses (5, 10, 20 and 40 mg/kg) were administered to these foals at 1 month of age. beta(po) (0.548 +/- 0.023 h-1) and F (68.26 +/- 2.43%) were not affected significantly by the size of the dose. Cmax was approximately doubled with each two-fold increase in dose: 3.15 +/- 0.15, 5.84 +/- 0.48, 12.17 +/- 0.93 and 19.71 +/- 2.19 micrograms/mL. Dose-dependent kinetics were observed in MRTpo, MAT, Ka and tmax.
为评估马驹年龄对头孢羟氨苄药代动力学的影响，选取5匹小马驹，分别在0.5、1、2、3和5月龄时给予单次静脉注射剂量（5mg/kg）和单次口服剂量（10或20mg/kg）的头孢羟氨苄。在重复测量分析中评估了终末消除速率常数（β(po)）、口服平均驻留时间（MRTpo）、平均吸收时间（MAT）、口服吸收速率常数（Ka）、生物利用度F、血清峰值浓度（Cmax）和达峰时间（tmax）等药代动力学参数。在不同动物年龄中，静脉注射剂量的参数在动物年龄间无显著变化（P≥0.05）。平均值±标准误为：β(IV)=0.633±0.038h-1；Cl=0.316±0.010L/kg/h；Vc=0.196±0.008L/kg；Varea=0.526±0.024L/kg；VSS=0.374±0.014L/kg；MRTiv=1.22±0.07h；Kel=1.67±0.08h-1。口服给药后，药物吸收随年龄增长而加快（P<0.05），这可通过MRTpo、MAT、Ka和tmax反映出来。然而，口服生物利用度（±标准误）从0.5月龄时的99.6±3.69%显著下降（P<0.05）至5月龄时的14.5±1.40%。为评估剂量对药代动力学参数的影响，在这些马驹1月龄时给予一系列口服剂量（5、10、20和40mg/kg）。β(po)（0.548±0.023h-1）和F（68.26±2.43%）不受剂量大小的显著影响。Cmax随剂量每增加一倍大约增加一倍：3.15±0.15、5.84±0.48、12.17±0.93和19.71±2.19μg/mL。在MRTpo、MAT、Ka和tmax中观察到剂量依赖性动力学。
