The effects of concurrent administration of either cimetidine 800 mg once daily or ranitidine 300 mg once daily on the single-dose pharmacokinetics of ritanserin 10 mg were investigated in an open, randomized three-way cross-over, controlled investigation in 9 healthy volunteers. Concurrent administration of cimetidine had no significant effect on the area under the plasma concentration-time curve of ritanserin compared with control experiments. The maximum plasma concentration of ritanserin was decreased significantly (105.0 +/- 9.2 versus 125.0 +/- 13.8 ng/mL; P = .0039), whereas time to reach maximal concentration (tmax) of ritanserin was only slightly but not significantly increased, if the subjects were pretreated with cimetidine. After concurrent ingestion of ranitidine, only a trend to a decrease in the maximum plasma concentration of ritanserin was observed. Time to achieve the maximum plasma concentration, terminal half-life of elimination, and the total area under the plasma concentration-time curve of ritanserin were not altered in comparison with control experiments. The results of the study show that concurrent treatment with cimetidine 800 mg once daily or ranitidine 300 mg once daily has no apparent effect on the systemically available amount of ritanserin after a single oral dose of 10 mg. Both H2-antagonists cause a significant (cimetidine) or borderline significant (ranitidine) decrease of the maximum plasma concentration of ritanserin and a slight but not significant increase in tmax (cimetidine). These effects are of minor clinical importance and seem most likely be due to a decrease of the rate of absorption of ritanserin during concurrent administration of cimetidine/ranitidine.