Loperamide in rat intestines: a unique disposition.

When everted sacs of rat duodenum, jejunum and ileum were incubated with [14C]loperamide in vitro, unchanged drug and its metabolites were found not only in tissues but also in media of the mucosal side with virtually no radioactivity in media of the serosal side. The amounts of metabolites found in media of the mucosal side were comparable to or larger than those in tissues. Di-desmethyl loperamide was more predominant in the media as compared with mono-demethylated one than in the tissues. Therefore, a portion of loperamide absorbed in intestines can be metabolized there and directly secreted back into lumen. Oral loperamide thus undergoes a unique disposition, likely constituting one of mechanisms for its distinct dissociation of central and antidiarrheal activities.