cilastatin--imipenem-drug-combination and Renal-Insufficiency

The pharmacokinetics of imipenem/cilastatin were determined in 7 critically ill patients undergoing slow hemodialysis (HD). All patients were anuric. Following intravenous administration of 500 mg of imipenem/cilastatin, concentrations of the drugs in the serum and dialysate were monitored during slow HD. The elimination phase half-life of imipenem was 3.1 +/- 0.3 h and that of cilastatin was 9.7 +/- 1.2 h. The total body clearance of imipenem and cilastatin was 84.0 +/- 7.2 and 32.2 +/- 2.4 ml/min, respectively. Clearance of imipenem and cilastatin during slow HD was 24.3 +/- 2.4 and 54.3 +/- 3.1%, respectively, of total body clearance. After the 10.5-h session of slow HD, serum concentrations of imipenem and cilastatin were 2.3 +/- 0.4 and 16.0 +/- 1.2 mg/l, respectively. It appears that at least 500 mg of imipenem may be needed as a supplemental dose after a session of slow HD or the application interval should be shortened to maintain a therapeutic concentration.

Topics: Aged; Cilastatin; Cilastatin, Imipenem Drug Combination; Critical Illness; Drug Combinations; Drug Evaluation; Drug Therapy, Combination; Female; Half-Life; Humans; Imipenem; Infusions, Intravenous; Male; Renal Dialysis; Renal Insufficiency