The pharmacokinetics and tissue penetration of imipenem.

Two studies were performed to investigate the penetration of imipenem into chemically induced inflammatory exudate and into peritoneal fluid. In the first study six volunteers received 500 mg of imipenem, alone and with 500 mg cilastatin. Little difference was noted in the pharmacokinetics or inflammatory fluid penetration of imipenem when given with or without cilastatin. The only significant alteration was the urine recovery (an increase from a mean of 14.7% to 55.6% in the presence of the enzyme inhibitor). The mean inflammatory fluid level of imipenem at 30 min was 6.2 mg/l (or 35% of the plasma level). The inflammatory fluid levels exceeded the plasma levels after 2 h. The overall penetration of imipenem/cilastatin into inflammatory fluid was 67.8% (+/- 13.8) and imipenem alone 73.2% (+/- 13.9). The mean elimination half-life of imipenem from plasma was 1.1 h and from inflammatory fluid 1.4 h (with or without cilastatin). In the second study, 29 patients received 1 g imipenem plus cilastatin before elective surgery and plasma and peritoneal levels were measured over 4 h. There was considerable penetration of the peritoneum, imipenem levels in excess of 30 mg/l being found 15 min after administration declining to 5-7 mg/l by 3-4 h. The mean percentage penetration was 73.4% (+/- 22.1). A brief review of the literature on imipenem tissue penetration is included.