<i>&beta;</i>-Adrenoceptor-Blocking Agents: Pharmacokinetic Differences and Their Clinical Implications Illustrated on Pindolol

J. Meier, PhD, Biopharmaceutical Department, Sandoz Ltd., CH-4002 Basel (Switzerland) Quite a number of j3-adrenoceptor-blocking drugs are available today for the treatment of hypertension and other cardiovascular disorders. Since ß-blockers are drugs which are used in chronic treatment, the question of their long-term efficacy and safety has been of great interest and concern. It is, therefore, justified to compare the pharmacokinetic properties of the most frequently studied substances: acebutolol, alprenolol, atenolol, labetalol, metoprolol, nado-lol, oxprenolol, penbutolol, pindolol, practolol, propranolol, sotalol and timolol. The pharmacokinetics of the Ø-blockers are important and relevant because there are clear relations between their plasma concentrations and their effects, e.g. in exercise-induced tachycardia (1, 2) and for antihypertensive effect (3). ‘Ideal’ Pharmacokinetics Since there are many Ø-blockers available with very similar pharmacological profiles, it is desirable to choose a /3-blocker with favorable or ideal pharmacokinetics due to the necessary chronic treatment – quite often in combination with many other drugs – and due to their frequent use in patients with other disorders like renal, hepatic or cardiac insufficiencies. Table I lists 12 pharmacokinetic criteria which can be anticipated for an ‘ideal’ substance. These criteria are based on ecological considerations of drug treatment (e.g. dosage, good absorption and oral bioavailability), on predictability and small variability of plasma levels (e.g. small first-pass effect, dose-linearity), on practical experimental conditions (methodologies, correlations with pharmacodynamics) and on Meier 2 Table I. Pharmacokinetic criteria for ideal drug Criterium Specific, sensitive bioanalitical methodology Once daily application possible Small daily dose ( < 50 mg/day) Good absorption ( > 80%) Small first-pass effect « 20%) High absolute oral bioavailability ( > 80%) Small or moderate protein binding ( < 80%) Known correlation between plasma levels and effects Linear pharmacokinetics valid