The disposition and metabolic fate of 14C-meropenem in man.
1. The metabolism and pharmacokinetics of 14C-meropenem were studied in five volunteers who received 0.5 g (40 microCi) of the radiolabelled drug by i.v. infusion. 2. The maximum concentration of drug in plasma was 27 +/- 2 micrograms/ml (70 microM) 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 micrograms/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.
Harrison
M P
MP
ZENECA Pharmaceuticals, Alderley Park, Macclesfield, Cheshire, UK.
Haworth
S J
SJ
Moss
S R
SR
Wilkinson
D M
DM
Featherstone
A
A
D000328:Adult; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D000077731:Meropenem; D008875:Middle Aged; D013845:Thienamycins / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D013845:Thienamycins; D000077731:Meropenem