【摘要】 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。更多还原

【Abstract】 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.更多还原