单剂量加替沙星口服在Beagle犬体内药代动力学研究

Pharmacokinetics of a single dose oral administration of gatifloxacin in Beagle dogs

目的:探讨加替沙星口服后在Beagle犬体内药代动力学特征。方法:选取12只Beagle犬分为三个剂量组,分别单剂给予加替沙星34 mg/kg1、7 mg/kg、8.5 mg/kg口服后0.5、1.0、2.0、4.0、6.0、8.0、12.0、24.0、36.0、48.0、60.0 h取血,高效液相色谱法测定血中药物浓度,3p97程序计算药动学参数。结果:大、中、小剂量组动物T1/2ka分别为(2.64±1.00)h、(1.43±0.90)h和(2.00±0.53)h;T1/2ke分别为(7.33±1.79)h(、6.32±3.28)h和(5.34±2.60)h;Tmax分别为(6.32±2.32)h(、5.77±1.62)h和(3.95±2.18)h;Cmax分别为(6.31±2.66)μg/mL(、2.67±0.64)μg/mL和(0.64±0.30)μg/mL;AUC0→60分别为(110.86±43.76)μg/(mL.h)、(41.93±5.58)μg/(mL.h)和(8.58±2.70)μg/(mL.h)。结论:加替沙星口服易吸收,血药浓度高,代谢较慢,有益于临床应用。

Objective： To study the pharmacokinetics of a single dose of oral gatifloxacin copasle in Beagle dogs. Methods： 12 Beagle dogs were divided into three groups with single dose of 34 mg/kg, 17 mg/kg and 8.5 mg/kg of gafifloxacin administrated respectively. The blood samples were taken at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0, 24.0, 36.0, 48.0, 60.0 hours after oral administration. The concentrations of gatifloxacin in plasma were determined by HPLC method. Pharmacokinetic parameters were calculated with 3p97 pharmacokinetic program. Results： Concentration-time curves of gatifloxacin fitted to one-compartment mode, T1/2ke was （7.33 ± 1.79）h, （6.32 ± 3.28） h, （5.34 ± 2.60）h respectively; T1/2ke （2.64 ± 1.00）h, （1.43 ± 0.90）h, （2.00 ± 0.53）h respectively; Tmax （6.32 ± 2.32）h, （5.77 ± 1.62）h, （3.95 ± 2.18）h respectively; Cmax （6.31 ± 2.66）μg/mL, （2.67 ± 0.64）μg/mL, （0.64 ± 0.30）μg/mL respectively. AUC0→∞ was （ 110.86 ± 43.76）μg/（mL· h）, （41.93 ± 5.58）μg/（mL·h）, （8.58 ± 2.70）μg/（mL·h） respectively. Conclusions. The oral gatifloxacln, which is good in clinic application, is rapidly absorbed and has high drug concentrations in blood and eliminated slowly.