Metabolism and pharmacokinetic studies of misoprostol.

Absorption, metabolism and excretion of radiolabelled misoprostol were studied in laboratory animals and in humans. Dog and man were similar in terms of key parameters examined. Misoprostol itself was not present in plasma after its oral administration to humans. Misoprostol was rapidly converted by de-esterification to its free acid. This metabolite possesses significant desired pharmacological activity. Further metabolic conversion occurs over time via beta-oxidation of the alpha side chain, omega-oxidation of the beta side chain and reduction to the prostaglandin F analogs. The serum protein binding of the free acid metabolite of misoprostol was similar in young (81-88%) and elderly (81-89%) people. Binding was concentration-independent and was not altered by drugs which one would expect to be co-administered with misoprostol. In the rat, misoprostol neither inhibited nor induced drug metabolizing enzymes. A radio-immunological assay for measurement of the free acid metabolite in human plasma has been developed. This method has a sensitivity of 23 pg/ml and appears to be sufficiently sensitive for use in clinical trials.