庆大霉素不同给药方案的药代动力学和肾功能损害的实验研究

目的研究庆大霉素(GTM)不同时辰给药方案对大鼠肾功能损害、血药浓度和药动学参数的影响。方法①大鼠分6组:对照组、时辰每日单次给药组N(活动期给药)100组、D(休息期给药)100组,分别于1:00和13:00给药100mg·kg-1,im]、时辰每日2次不等量给药组和传统每日2次等量给药组(N90+D10组、N70+D30组、N50+D50组,每日1∶00和13∶00分2次im90mg·kg-1+10mg·kg-1、70mg·kg-1+30mg·kg-1、50mg·kg-1+50mg·kg-1)。各组分别于给药d1、10和20测定血清肌酐(Cr)、血清尿素氮(BUN)。②给药后0.25、0.5、1、2、5和8h分别于眼眶取血,测定血药浓度,给药d10、20重复上述采血过程。绘制药时曲线,计算药动学参数。结果①肾功能损害:给药d10,N50+D50组Cr和BUN水平最高,与给药d1和同期对照组相比差异有显著性(P<0.05);N100组最低,与同期对照组相比差异有显著性(P<0.05)。血药浓度:给药d10,N100组和D100组峰浓度差异有显著性(P<0.05)。给药d20,N50+D50组峰浓度高于两次不等剂量组峰浓度,但差异无显著性。③药动学参数:给药d20,N50+D50组CLs最小,N100组最大,给药d1、10、20,N100组T12最短,N50+D50组T12最长(P<0.05)。结论在时辰给药方案中,GTM以活动期单次给药肾功能损害最小,血药峰浓度低,T12最短,CLs最大。

An experimental study of pharmacokinetics and impairment of renal function with different dosage regimens of gentamicin in rats

Aim To study effects of different dosage regimens of gentamicin(GTM) on impairment of renal functions, plasma concentrations and pharmacokinetics in rats. Method 108 rats were divided into 6 groups: control group; chronological once-daily dose groups (N100 and D100 group, in which 100 mg·kg -1 GTM were intramuscularly administrated at 01 ∶00 or 13 ∶KG-*3]00 respectively), and chronological twice-daily different dose groups (N90+D10, N70+D30, N50+D50 group, in which 90 mg·kg -1+10 mg·kg -1, 70 mg·kg -1+30 mg·kg -1 and 50 mg·kg -1+50 mg·kg -1 GTM were given at 1:00 and 13:00 respectively). The blood urea nitrogen (BUN) and creatinine (Cr) levels were observed, the plasma concentrations of GTM at 0.25,0.5,1, 2, 5 and 8h were determined, the C-T curves were profiled and the pharmacokinetic parameters were calculated at the 1st, the 10th, and the 20th day of administrations. Results ① Impairment of renal function. At the 10th day of administration, the Cr and BUN levels of N50+D50 group were the highest. There was a significant difference when compared those of the 10th day of administration with those of the 1st day of administration and of control group at same time respectively (P<0.05). The Cr and BUN levels of N100 group on the 10th day were the lowest among all experimental groups. There was a significant difference when compared those of the 10th day administration with those of the 1st day of administration and of the control group at same time respectively (P<0.05). ② Plasma concentrations: Significant difference of peak concentrations existed between the once daily groups (N100 and D100, P<0.05) at the 10th day of administration. ③ Pharmacokinetic parameters: At the 20th day of administration, the CLs of N50+D50 group was the smallest, while that of N100 group was the largest. At the 1st, the 10th and the 20th day of administration, T_ 12 of N100 group was the shortest while that of N50+D50 group was the longest (P<0.05). Conclusions In chronological dosage regimens of gentamicin, the impairment of renal function was the least and the pharmacokinetic parameters were the most optimal when dosing at active phase in rats.