Clinical pharmacokinetics of doxazosin in a controlled-release gastrointestinal therapeutic system (GITS) formulation

摘要

AimsA controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin mesylate, a long-acting selective α1-adrenoceptor antagonist, was developed to enhance the pharmacokinetic profile and simplify the titration schedule by precisely controlling drug delivery rate, permitting an initial dose of 4 mg once daily, compared with standard doxazosin, which is initiated at 1 mg day⁻¹ and titrated to a higher therapeutically effective dose. The aim of the present work was to evaluate the pharmacokinetics and bioavailability of doxazosin GITS with respect to the effect of food, age and gender, and multiple dosing. In addition, in vitro performance was assessed in conditions simulating the gastrointestinal environment.