Pharmacokinetics and analgesic effect of pethidine (meperidine) and its metabolites in the rat.

The pharmacokinetics of pethidine (meperidine) and norpethidine (normeperidine) have been investigated after iv administration of pethidine in the rat. The plasma concentration-time curve for pethidine could be described by a triexponential function. The calculated half-lives were 6.0, 18.5, and 64.5 min. Norpethidine, metabolically formed from pethidine, reached maximum plasma concentrations after 30 min and declined biexponentially with half-lives of 66.8 and 301 min. The time course of analgesia after iv administration of pethidine, norpethidine, and p-hydroxypethidine has also been evaluated. When the pharmacokinetic data were compared with the time course of analgesia, the plasma levels of pethidine could be correlated with the analgesic effect after the first rapid distribution phase. The pharmacokinetic constants for pethidine and norpethidine were used to stimulate the plasma levels of these compounds after multiple doses of pethidine. Accumulation of norpethidine was demonstrated to occur, which may be of importance when toxic and analgesic effects of pethidine are evaluated.