妥布霉素在腹透患者中的药代动力学及给药方案探讨

THE STUDY OF TOBRAMYCIN PHARMAC0KINETICS DURING PERITONEAL DIALYSIS AND DOSAGE REGIMENS

在7例间歇腹膜透析(IPD)患者中进行妥布霉素药代动力学研究。单剂量40mg妥布霉素1次灌入腹腔后,用微量微生物法测定血液及透析液浓度。3h中约有53.2%的妥布霉素自腹腔吸收,平均最高血药浓度为1.5μg/ml。按双室模型计算结果,平均Ka=0.8163h^(-1),K_(10)=0.02907h^(-1),K_(12)=0.1363h^(-1);K_(21)=0.2616h^(-1);t1/2(β)=53.8h;12h透析液中仅排出12%妥布霉素。根据药代动力学参数,作者提出腹腔感染时拟采用20～40mg bid IP的给药方案,5例患者使用结果,证明该给药方案可使腹腔局部维持较高的杀菌浓度而周围血中则保持相对较低浓度,对腹腔感染治疗极为有利有效。

The pharmacokinetics of tobramycin were examined in7 patients with renal failure maintained by interienal peritoneal dialy-sis (IPD). After a dose of 40mg tobramycin given interperitoneally, the concen-tion of serum and dialysate were measured by agar diffusion technique.About 53. 2% of the unchanged drug which administered was absorbed byperitoneum in 3 hours, the mean Cmax was 1 .5μg/ml. The results showedthat the following parameters: Ka= 0. 8163h^(-1), K_(10) = 0. 02907h^(-1), K_(12)=0. 1363h^(-1), K_(21) = 0. 2616h^(-1), t1/2=53. 8h, it is only 12% tobramycin removed bydialysis in 12 hours. To be basis on this pharmacokinetic parameters, theregimen of 20-40mg/21 bid ip, in peritonitis was recommend,the serum and dialy-sate concentration were determined after tobramycin was given with 40mg interperitonilly twice a day in 5 patiets for 3 days. That dose wouldprovide steady-state serum concertration about 2 μg/ml, with a higherlevel of peritoneal dialysate (2-9μg/ml). These date could be useful intreating IPD patiets who have peritonitis.