Pharmacokinetic and Pharmacodynamic Comparison of Controlled-Release Carvedilol and Immediate-Release Carvedilol at Steady State in Patients with Hypertension

摘要: Carvedilol is indicated for the treatment of essential hypertension and mild-to-severe chronic heart failure, as well reduction cardiovascular mortality in clinically stable post–myocardial infarction patients with left ventricular dysfunction. a racemic mixture R(+) S(−) enantiomers that combines β 1 -, 2 α -adrenoceptor blockade. For all indications, immediate-release (IR) formulation carvedilol taken twice daily. A controlled-release (CR) allows once-daily dosing has recently been developed. In this double-blind, parallel-group, crossover study, 122 were randomly allocated to receive low high doses or placebo. Patients received either constant dose (CR 20 mg once daily IR 6.25 daily) titrated 80 25 before being crossed over an equivalent alternative formulation. The pharmacokinetic (PK) pharmacodynamic (PD) profiles compared between receiving CR IR. PK R(+)- S(−)-carvedilol formulations (based on area under curve, maximum plasma concentration [C max ], trough drug concentration). Consistent extended-release formulation, delayed C by 3.5 hours both IR, attenuation exercise-induced rate was maintained entire 24-hour period, demonstrated -blocking effects at (end interval [PD min ]), suggesting absorption does not interfere PD effect. first direct comparison subjects hypertension, fewer adverse events reported while (59.1% overall) (77.5% overall). This true regardless received. Headache most commonly event Importantly, dizziness headache less often when CR. study show had comparable -adrenergic blockade steady-state conditions. Notably, provides consistent 24 dose.