Abstract
The metabolism and disposition of meropenem (MEPM) were studied in rats dosed with an intravenous administration of 14C labeled or unlabeled MEPM.
After the intravenous administration of [14C] MEPM, the radioactivity was rapidly and widely distributed to all tissues except the brain. The highest concentrations of radioactivity were detected in the kidneys. Elimination was very rapid and there was no marked retention of radioactivity in any specific tissue. The plasma concentrations of MEPM declined rapidly, with a half-life of about 7 minutes. The radioactivity was excreted very rapidly, with nearly 90% of the dose being excreted in urine within 6 hours after dosing. Fecal and biliary excretion were minor routes of excretion in rats.
Plasma profiles of MEPM after 3 months of daily doses were similar to those after a single administration. There was a linear dose response of plasma concentration on days 1 and 92.
The radioactivity was detected both in embryos and milk, albeit at very low concentrations.
Following 14 days of daily intravenous doses, MEPM produced no effect on the hepatic microsomal mixed function oxidase enzymes.
The fate of [14C] MEPM in rats with hepatic dysfunction was not so different from that in normal rats. However, in rats with renal failure, a prolonged plasma half-life of radioactivity and delay of excretion were observed. In elderly rats, a higher plasma concentration of radioactivity and a prolonged plasma half-life were observed.
