Somani P, Shapiro R S, Stockard H, Higgins J T
Clin Pharmacol Ther. 1982 Jul;32(1):113-21. doi: 10.1038/clpt.1982.134.
Gentamicin kinetics were determined after intravenous or intraperitoneal injection in five patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Our objective was to determine rate of absorption of gentamicin from the peritoneum into the systemic circulation and vice versa. After intraperitoneal instillation of 1 mg/kg in the CAPD fluid during a 6-hr dwell time, the antibiotic appeared in the serum within 15 min in four of five patients. Peak serum concentrations ranged between 1.6 and 7.2 mg/l(mean +/- SD = 3.52 +/- 2.22) in all five patients and the time to reach peak concentration was 3.8 +/- 1.5 hr. Peritoneal gentamicin clearance was 13 ml/min. Percent extraction of gentamicin from the PD fluid within the 6 hr of intraperitoneal exposure ranged from 65% to 100% (mean +/- SD = 86.8 +/- 13.2). The fraction of the intraperitoneal dose absorbed into systemic circulation was found to be 0.84 independently by calculating the ratio of AUCip and AUCiv. When the same dose of gentamicin was injected intravenously (1 mg/kg), no gentamicin could be detected in the peritoneal fluid in three of five patients and only a very small amount of the drug was present for a brief period of time in the remaining two. The kinetic parameters of intravenous gentamicin were: volume of distribution, 0.3 l/kg; elimination rate constant, 0.028 hr(-1), plasma clearance 0.009 l/kg . min(-1), and half-life 27.4 hr. In two patients with acute peritonitis treated with intraperitoneal gentamicin, peak serum concentrations were found to range between 3.5 and 4.5 mg/l. These data suggest that gentamicin is rapidly absorbed from the peritoneal fluid into the blood compartment, but that occurrence of the reverse exchange is negligible. Thus, CAPD would not be expected to alter the elimination characteristics of intravenous gentamicin. Instillation of gentamicin in CAPD fluid may allow rapid absorption to reach therapeutic serum concentrations.
对5例持续性非卧床腹膜透析(CAPD)患者进行静脉或腹腔注射后,测定庆大霉素的动力学。我们的目的是确定庆大霉素从腹膜吸收进入体循环的速率,反之亦然。在CAPD液中腹腔内滴注1mg/kg,停留6小时期间,5例患者中有4例在15分钟内血清中出现抗生素。所有5例患者的血清峰值浓度在1.6至7.2mg/L之间(平均值±标准差=3.52±2.22),达到峰值浓度的时间为3.8±1.5小时。腹膜庆大霉素清除率为13ml/分钟。腹腔内暴露6小时内从腹膜透析液中提取庆大霉素的百分比在65%至100%之间(平均值±标准差=86.8±13.2)。通过计算AUCip与AUCiv的比值,独立发现腹腔内剂量吸收进入体循环的分数为0.84。当静脉注射相同剂量的庆大霉素(1mg/kg)时,5例患者中有3例在腹膜液中未检测到庆大霉素,其余2例在短时间内仅存在极少量药物。静脉注射庆大霉素的动力学参数为:分布容积0.3L/kg;消除速率常数0.028小时-1,血浆清除率0.009L/kg·分钟-1,半衰期27.4小时。在2例用腹腔内庆大霉素治疗的急性腹膜炎患者中,血清峰值浓度在3.5至4.5mg/L之间。这些数据表明,庆大霉素可迅速从腹膜液吸收进入血室,但反向交换的发生率可忽略不计。因此,预计CAPD不会改变静脉注射庆大霉素的消除特性。在CAPD液中滴注庆大霉素可使药物迅速吸收,达到治疗性血清浓度。