Safety and tolerability of multiple doses of imipenem/cilastatin.
The safety and tolerability of 1 gm imipenem and cilastatin given together every 6 hours for 10 days was evaluated in a randomized, double-blind, placebo-controlled trial in normal subjects. Nausea was more common in the drug-treated group (five of six subjects) than in the control group (two of six subjects). No consistent changes in hepatic function indices were noted. Although beta 2-microglobulin excretion showed a significant trend of rising over time in the drug group, there were no differences between groups with regard to 24-hour urinary excretion of either N-acetyl-beta-glucosaminidase or beta 2-microglobulin. Urinalysis did not reveal any casts and serial creatinine clearance determinations showed no change in renal function in either the drug- or placebo-treated groups. Pure tone audiograms were performed before and after dosing in 11 of 12 subjects; no changes were noted. We conclude that the combination of imipenem and cilastatin was well tolerated and safe.
D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000704:Analysis of Variance; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001806:Blood Urea Nitrogen; D015377:Cilastatin; D003404:Creatinine / Q000378:metabolism; D003521:Cyclopropanes / Q000009:adverse effects / Q000494:pharmacology*; D004311:Double-Blind Method; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D006801:Humans; D015378:Imipenem; D007677:Kidney Function Tests; D008111:Liver Function Tests; D008297:Male; D011863:Radioimmunoassay; D011897:Random Allocation; D012709:Serum Albumin; D013845:Thienamycins / Q000009:adverse effects / Q000494:pharmacology*; D001613:beta 2-Microglobulin / Q000652:urine
D003521:Cyclopropanes; D012709:Serum Albumin; D013845:Thienamycins; D001613:beta 2-Microglobulin; D015377:Cilastatin; D015378:Imipenem; D003404:Creatinine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000118:Acetylglucosaminidase; D001663:Bilirubin