Pharmacokinetics of beta-adrenoceptor blocking agents: clinical significance of hepatic and/or renal clearance.

A great number of beta-adrenoceptor blocking drugs are now available for clinical use which show great differences with respect to their pharmacokinetic properties. Bioavailability might be low because of a low absorption rate after oral application in the case of hydrophilic drugs like atenolol or might be low because of a high first-pass effect in the liver in the case of metoprolol or propranolol. Plasma levels of these latter drugs may vary considerably and inhibition of their oxidative metabolism by cimetidine may lead to an increase of peak plasma concentrations. In general, lipophilic beta-blockers are metabolized in the liver whereas hydrophilic agents are eliminated in the kidneys as unchanged drugs. Dose has to be adjusted according to renal function in the case of atenolol, carteolol, nadolol, sotalol and acebutolol, which is transformed into the active metabolite diacetolol. Drugs like bisoprolol, betaxolol and pindolol are eliminated via the liver and the kidneys. Bisoprolol, for example, shows a balanced clearance as it is eliminated to about 50% in the liver and 50% via the kidneys. Failure of one clearance organ (liver, kidney) leads to a maximally twofold increase in plasma half-life of bisoprolol. Being aware of the observation that some drugs show a long terminal half-life, it has been demonstrated that plasma levels correlate to duration of action. This is of major importance for the treatment of coronary heart disease as a once-daily dose should be active for 24 h.