Pharmacokinetics of benzodiazepines: metabolic pathways and plasma level profiles

Abstract

Large differences exist among the various benzodiazepines with regard to their pharmacokinetic properties and metabolism in man. Some are eliminated from the body at a relatively slow rate, e.g. desmethyldiazepam, and others are metabolized rapidly, e.g. midazolam, triazolam. Several benzodiazepines have major active metabolites that are slowly eliminated, e.g. medazepam, halazepam , quazepam and, consequently, should be considered as potentially long-acting. Such differences may be very important clinically because pharmacokinetic data will help to optimize drug therapy with respect to the choice of the proper drug and drug preparation, as well as with the choice of a proper dose and dosage regimen. The therapeutic objectives of drug therapy differ quite considerably for the various clinical indications of benzodiazepines. In anti-anxiety and anti-epileptic therapy, prolonged or continuous treatment is pursued, so that compounds with relatively long or intermediate elimination half-lives of parent drug or active metabolites are of advantage. In hypnotic treatment, on the other hand, the duration of drug action should be restricted to the duration of the night, hence a compound with a short elimination half-life may be preferred. An overview is given of the pharmacokinetics of the major benzodiazepines currently available and of some interesting new ones that are still in the development stage.