Inverse PK/PD: estimation and differentiation of bioavailability from effect kinetics--observations with beta-adrenoceptor antagonists.
The time course of pharmacodynamic effects allow to resolve bioavailability relevant pharmacokinetic information, provided simple assumptions can be made about their interrelation. This approach furthermore allows to differentiate ancillary properties of chemically distinct pharmacological agents on the basis of their mutual pharmacodynamic actions. The advantages and pitfalls of this strategy are discussed here for beta-adrenoceptor antagonists on the basis of their pharmacodynamic characterization by the extent of their binding ability to ex vivo in vitro beta-adrenoceptors (RRA assay) and their blunting effects on the ergometric rise in heart rate.
De Mey
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IPHAR Institute for Clinical Pharmacology, Höhenkirchen-Siegertsbrunn, Germany.
D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000328:Adult; D001667:Binding, Competitive; D001682:Biological Availability; D002227:Carbazoles / Q000493:pharmacokinetics / Q000494:pharmacology; D000077261:Carvedilol; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008954:Models, Biological; D011412:Propanolamines / Q000493:pharmacokinetics / Q000494:pharmacology; D011433:Propranolol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D016032:Randomized Controlled Trials as Topic; D013610:Tachycardia / Q000188:drug therapy
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D011433:Propranolol