Abstract
The metabolism and disposition of meropenem (MEPM) were studied in dogs and monkeys dosed with an intravenous administration of 14C labeled or unlabeled MEPM.
After the intravenous administration of [14C] MEPM to dogs, 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 rapid and there was no marked retention of radioactivity in any specific tissue. The plasma concentrations of MEPM declined rapidly, with an initial half-life of about 5 minutes and a terminal half-life of about 40 minutes. Excretion of radioactivity was rapid and entire radioactivity (100%) was excreted in urine within 24 hours after dosing. The majority of radioactive components in urine corresponded to unchanged MEPM (72.1%) and the metabolite corresponding to the ring-opened form H-4295 (22.1%).
The plasma profile and urinary excretion of MEPM after 14 days of daily doses were similar to those after a single administration.
After the intravenous administration of [14C]MEPM to monkeys, plasma concentrations of MEPM declined rapidly, with an initial half-life of about 12 minutes and a terminal half-life of about 30 minutes.
