Influence of magnesium and aluminum hydroxide mixture on chlordiazepoxide absorption

Abstract

Ten healthy male subjects ingested 25 mg of chlordiazepoxide hydrochloride (Librium) with 100 ml of water or with 100 ml of magnesium and aluminum hydroxide (Maalox) in a single-dose crossover study. Multiple venous blood samples drawn during the first 24 hr after each dose were assayed for concentrations of chlordiazepoxide and its major metabolite, desmethylchlordiazepoxide. The antacid prolonged the mean chlordiazepoxide absorption half-time from 11 to 24 min, and in 6 of 10 subjects delayed achievement of the peak blood concentration by from 0.5 to 3.0 hrs. The formation of desmethylclordiazepoxide was also slowed. The areas under the 24 hr blood concentration curve for chlordiazepoxide and for its metabolite were not influenced by the antacid. The apparent elimination half-life of chlordiazepoxide (8.4 and 8.2 hr) was not significantly affected. Administration of chlordiazepoxide with antacid reduces the rate of its absorption but does not alter the completeness of absorption or the apparent rate of elimination.