On the pharmacokinetics of domperidone in animals and man II. Tissue distribution, placental and milk transfer of domperidone in the Wistar rat

Abstract

Tissue distribution, placental transfer and transition into milk of the gastrokinetic drug domperidone were studied in the Wistar rat after i.v. or p.o. administration of the labelled compound at 2.5 mg/kg. Whole-body autoradiography and liquid scintillation counting were used to investigate the tissue localization of domperidone in pregnant and non-pregnant rats. In fasted rats, tissue levels were maximal within 15 minutes after either route. In non-fasted animals peak time occurred 30 minutes after oral treatment. Large amounts of radioactivity were present in the stomach, and in the bilious contents of the intestine. High activity was further detected in the liver, kidney, lung and some glandular tissues. After a rapid initial decrease radioactivity was eliminated with a half-life of 8-10 hours. Except for brain and testes, plasma levels were markedly lower than corresponding tissue levels. At 1 hour placental levels were 2-2.7 times higher and foetal concentrations 2.1-2.5 times lower than maternal plasma levels. The placentae and foetuses predominantly contained unchanged domperidone. At peak time only 0.2 (i.v.) and 0.08% (p.o.) of the dose crossed the placenta. Blood levels were always lower than milk concentrations. Preferentially metabolites were excreted with the milk. After a 20-hour suckling period of orally dosed dams, 0.2% of the dose was recovered in the combined tissues of 6 suckling pups.