Pharmacokinetic optimisation of therapy with beta-adrenergic blocking agents.

beta-Adrenergic blockade has provided one of the major pharmacotherapeutic advances of this century. The drugs in this class have the common property of blocking the binding of catecholamines to beta-adrenergic receptor sites; however, there are pharmacodynamic and pharmacokinetic differences between the individual agents which are of clinical importance. Among these differences are the completeness of gastrointestinal absorption, degree of hepatic first-pass metabolism, lipid solubility, protein binding, brain penetration, concentration within cardiac tissue, rate of hepatic biotransformation, and renal clearance of drug and/or metabolites. Long-acting formulations of existing beta-blockers are currently in use, and ultrashort-acting agents are also available. The pharmacokinetics of beta-blocking drugs can also be influenced by race, age, cigarette smoking and concomitant drug therapy. The wide interpatient variability in plasma drug concentration observed with beta-blockers makes this parameter unreliable in routine patient management. Despite the pharmacokinetic differences among the beta-blockers, these drugs should always be titrated in the individual patient to achieve the desired clinical response.