Unidirectional absorption of gentamicin from the peritoneum during continuous ambulatory peritoneal dialysis

Abstract

Gentamicin kinetics were determined after i.v. or i.p. injection in 5 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). The objective was to determine rate of absorption of gentamicin from the peritoneum into the systemic circulation and vice versa. After i.p. instillation of 1 mg/kg in the CAPD fluid during a 6-h dwell time, the antibiotic appeared in the serum within 15 min in 4 of 5 patients. Peak serum concentrations ranged between 1.6-7.2 mg/l .hivin.x .+-. SD = 3.52 .+-. 2.22) in all 5 patients and the time to reach peak concentration was 3.8 .+-. 1.5 h. Peritoneal gentamicin clearance was 13 ml/min. Percent extraction of gentamicin from the PD fluid within the 6 h of i.p. exposure ranged from 65-100% (.hivin.x .+-. SD = 86.8 .+-. 13.2). The fraction of the i.p. dose absorbed into systemic circulation was 0.84 by independent calculation of the ratio AUC[area under the curve]ip and AUCiv. When the same dose of gentamicin was injected i.v. (1 mg/kg), no gentamicin could be detected in the peritoneal fluid in 3 of 5 patients and only a very small amount of the drug was present for a brief period of time in the remaining 2. The kinetic parameters of i.v. gentamicin were as follows: volume of distribution, 0.3 l/kg; elimination rate constant, 0.028 h-1; plasma clearance 0.009 l/kg .cntdot. min-1; and half-life 27.4 h. In 2 patients with acute peritonitis treated with i.p. gentamicin, peak serum concentrations ranged between 3.5-4.5 mg/l. Gentamicin is rapidly absorbed from the peritoneal fluid into the blood compartment, but occurrence of the reverse exchange is negligible. CAPD would not be expected to alter the elimination characteristics of i.v. gentamicin. Instillation of gentamicin in CAPD fluid may allow rapid absorption to reach therapeutic serum concentrations.