PHARMACOKINETIC EVALUATION OF IMIPENEM COMBINED WITH CILASTATIN IN CYSTIC-FIBROSIS

The pharmacokinetics of imipenem (MK-787) and cilastatin (MK-791) were studied in 30 patients with cystic fibrosis (CF) receiving the drug f or therapeutic purposes at doses of 11 mg/kg given as a 30-min infusio n. The serum concentrations and urine elimination were studied after t he first dose and during steady state. The concentrations were assayed by high-pressure liquid chromatography. The total areas under the imi penem serum concentration curves (AUCs) to infinity were 30.4+/-6.8 mg .h/l after the first dose compared with 29.1+/-7.1 mg.h/l during stead y state (NS). The cilastatin AUCs on the 2 days were 40.3+/-9.3 and 38 .3+/-0.4 mg.hA (NS), respectively. The urinary recovery of imipenem wa s 47.8+/-17.8% after the first dose and 57.8+/-24.2% during steady sta te (NS). The amounts of cilastatin eliminated in the urine during 6 h were 6/7.3+/-22.9% after the first dose and 60.5+/-17.0% of the dose d uring steady state (NS). The mean half-life of imipenem in these CF pa tients was 1.2+/-0.4 h on the first day of the examination and within the same range during steady state. The distribution volume (V(dbeta)) Was in the range of 28 liters, the total body clearance was 16.3 lite rs/h (285 ml/min) on the first day. The t1/2 of cilastatin was 0.59+/- 0.14 h after the first dose and 0.61+/-0.14 h during steady state. Thu s patients with CF eliminated cilastatin more quickly than imipenem.