Impaired Absorption of Chlorpromazine in Rats Given Trihexyphenidyl

1 The absorption and tissue distribution of orally administered [14C]-chlorpromazine (CPZ) were compared in trihexyphenidyl (THP; Artane)-treated and control rats. 2 Total radioactivity (CPZ) in the plasma and brain of rats treated with THP was significantly lower whereas total radioactivity in the stomach was significantly higher than in rats not previously treated with THP. 3 Gastric emptying in rats treated with THP was significantly delayed as measured by gastric clearance of a marker [14C]-polyethylene glycol. 4 Transport of [14C]-CPZ in everted sacs was not affected by treatment with THP. 5 Metabolism of [14C]-CPZ by liver homogenates was not affected by treatment with THP. 6 The relationship of delayed gastric emptying in THP-treated rats and their lower plasma and brain levels of [14C]-CPZ after oral administration is discussed.