GASTROINTESTINAL DISTRIBUTION OF THE PRODRUG LOPERAMIDE OXIDE AND ITS ACTIVE DRUG LOPERAMIDE IN THE DOG

Loperamide oxide Is a prodrug of the effective antidiarrheal loper-amide. Administration of this prodrug improves efficacy and toler-ability. For better understanding of these effects, the absorption and gastrointestinal distribution of loperamide oxide and of its active drug loperamide were studied. Beagle dogs received a sin-gle oral dose of Ioperamide oxide or loperamide at 0.16 mg/kg. Plasma, gastrointestinal contents and tissues, and some other organs were obtained. Concentrations were determined by spe-cffic radioimmunoassays. Loperamide oxide was gradually con-verted to loperamide In the gastrointestinal tract After administra-tion of the rug, the systemic absorption of the active drug was lower and more delayed than after administration of loperamide itself. As a consequence, more loperamide was available in the contents and the mucosa of the gut, in particular in the lower part of the small intestine and in the large intestine. The higher levels o