Pharmacokinetics and tolerance of N-formimidoyl thienamycin (MK0787) in humans.
The pharmacokinetics of intravenously administered N-formimidoyl thienamycin (MK0787) were studied in 14 healthy male subjects in a single-dose study, in which the volunteers received N-formimidoyl thienamycin with and without probenecid, and in a multiple-dose study, in which the subjects were given 250 or 500 mg every 8 h for 10 doses. High dose-related plasma concentrations of N-formimidoyl thienamycin were achieved; co-administration with probenecid resulted in only minor increases in these concentrations. No accumulation in plasma was seen after multiple doses. The plasma half-life of N-formimidoyl thienamycin was slightly less than 1 h and did not increase significantly with the coadministration of probenecid. The urinary recovery of N-formimidoyl thienamycin varied between 6.0 and 38.4% of the dose with a marked intersubject variability. Variations in individual subjects were small, however, when the urinary recoveries after repeated doses were compared. These results were in agreement with previous animal studies showing a renal metabolism of N-formimidoyl thienamycin. Probenecid administration resulted in a marked decrease in N-formimidoyl thienamycin urinary recovery. In vitro experiments showed that the decay of N-formimidoyl thienamycin in spiked pretreatment urine samples was 2 to 5%/h with more rapid degradation at acidic than at basic pH.
D000328:Adult; D000900:Anti-Bacterial Agents / Q000378:metabolism*; D004355:Drug Stability; D006801:Humans; D015378:Imipenem; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011339:Probenecid / Q000494:pharmacology; D013845:Thienamycins / Q000009:adverse effects / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D013845:Thienamycins; D015378:Imipenem; D011339:Probenecid