INFLUENCE OF CHOLESTYRAMINE ON THE PHARMACOKINETICS OF CERIVASTATIN

The possible influence of the bile acid sequestering agent cholestyram ine, a basic comedication in hypercholesterolemic patients, on the pha rmacokinetics of the new HMG-CoA reductase inhibitor cerivastatin was investigated. When both drugs were administered concomitantly in the m orning under fasting conditions, a decrease in relative bioavailabilit y by 21% could be observed, possibly due to irreversible adsorption of the statin to the resin. In addition, the delay in absorption led to a 41% decrease in cerivastatin mean maximum plasma concentration which also occurred at later time. A second study addressed in detail the q uestion of time interval required between both treatments to minimize the influence of cholestyramine pretreatment on cerivastatin bioavaila bility: dosing of cerivastatin at dinner (6 p.m.) or bed time (10 p.m. ) with cholestyramine pretreatment 1 hour before meal (5 p.m.) in both treatments. The decrease in mean AUC was now approximately 8 - 16% de pending on the time of pretreatment (1-hour-interval: 16%, 5-hour-inte rval: 8%), and C-max decreased by approximately 32%, irrespective of t he time of pretreatment. T-max was increased in both treatments, where as tin was not changed. The presented data support the conclusion that when administered concomitantly, the bioavailability of cerivastatin is moderately reduced by adsorption to cholestyramine. Following, howe ver, the dosing instructions of both cholestyramine (1 hour before mea l) and cerivastatin (once-daily in the evening at dinner or at bed tim e), i.e. administering both drugs several hours (at least 1 hour) apar t, the observed effects on rate and extent of absorption of cerivastat in are unlikely to be of clinical relevance.