Wehling Martin
Clinical Pharmacology Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Arzneimittelforschung. 2010;60(2):57-63. doi: 10.1055/s-0031-1296249.
Betablockers still represent widely prescribed drugs as they cover a wide spectrum of cardiovascular indications. Obviously, it is not trivial which betablocker to choose as they differ both with regard to their pharmacodynamic (e. g. selective vs. nonselective, beta vs. beta + alpha blocking activities) and pharmacokinetic profiles. Latter is largely governed by the metabolic properties, and, thus, their excretion route (renal or biliary route in unchanged or metabolized form). In the elderly population, the stability of plasma concentrations is particularly essential as this population has smaller compensatory tolerance to concentration variations than younger patients. The interaction potential of betablockers with regard to drug-drug, gene polymorphism-drug, excreting organ-drug interactions varies widely between individual substances. Compounds predominantly metabolized by polymorphic cytochromes such as CYP 2D6 are affected by the metabolizer status and competing compounds utilizing the same metabolic pathways can strongly influence plasma levels (examples metoprolol [CAS 37350-58-6], carvedilol [CAS 72956-09-3]). On the other hand, metabolically stable compounds which are predominantly excreted renally may be unfavourable as their plasma concentrations largely depend on renal function which may be blunted in elderly patients. The prototype of this category, atenolol (CAS 29122-68-7), has been associated with inferior results in mortality trials in hypertension treatment. Thus, a favourable compound should be partially stable in regard to metabolism to depend less on drug-drug and gene-drug interactions, but also utilize more than one routes of excretion, meaning both the direct renal and the metabolic routes. The prototype for this type of betablocker is bisoprolol (CAS 66722-44-9).
