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Abstract
1. The metabolism and pharmacokinetics of 14C-meropenem were studied in five volunteers who received 0-5 g (40 μCi) of the radiolabelled drug by i.v. infusion.
2. The maximum concentration of drug in plasma was 27 ± 2μg/ml (70 μM) corresponding to 98% of plasma radioactivity at the end of a 30 min infusion. The elimination half-life for meropenem in plasma was 1 h and meropenem remained the major radioactive component up to 6 h, but represented a decreasing proportion of the plasma radioactivity with time. One metabolite (the ring-open lactam) accounted for most of the remaining plasma radioactivity. The maximum concentration of metabolite was 1 ± 0.1 μg/ml and the concentration of total radioactivity decreased to 2% of the peak value by 8 h.
3. Over the 5 days of the study, urinary excretion of radioactivity accounted for 99 ± 0.5% dose, most of which was recovered in the first 8 h. There was negligible excretion in faeces.
4. Structural confirmation of the drug-related components in urine was accomplished by h.p.l.c.-mass spectrometry. Meropenem accounted for 71 ± 2% dose of 14C and the ring-open lactam metabolite for most of the remainder, no other metabolites were detected.
5. Meropenem was the major radioactive component in urine up to 8 h after dosing and is therefore remarkably stable to human renal dehydropeptidase (DHP-1) compared with other carbapenems in clinical use.