Comparative pharmacokinetics and pharmacodynamics of amlodipine in hypertensive patients with and without type II diabetes mellitus.

Recent clinical trials aimed at attenuating complications in diabetes mellitus have generated interest in the impact of drug formulation and altered pharmacokinetics and pharmacodynamics in diabetes. Specifically, it has been proposed that the diabetic state may alter the pharmacokinetics of several cardiovascular drugs, including some calcium antagonists. The present study investigates the effects of diabetes mellitus on the pharmacokinetics and pharmacodynamics of amlodipine in hypertensive subjects with and without diabetes mellitus to determine whether the diabetic state alters these parameters. This trial consisted of a 2-week placebo washout phase, a 2-week titration phase, and a 2-week maintenance phase. Study patients included 18 hypertensive patients with type II diabetes mellitus and 10 nondiabetic hypertensive patients. Blood samples were collected after administration of amlodipine and AUC, Cmax, and tmax were determined. The acute 24-hour pharmacodynamic response to amlodipine was assessed by blood pressure and telemetric heart rate measurements. There were no significant differences for either amlodipine 5 or 10 mg in AUC (p = 0.40 for 5 mg; p = 0.59 for 10 mg), Cmax (p = 0.41 for 5 mg; p = 0.45 for 10 mg), and tmax (p = 0.79 for 5 mg; p = 0.67 for 10 mg) between diabetic and nondiabetic hypertensive subjects. Similarly, the 24-hour pharmacodynamic effects of amlodipine on systolic blood pressure, diastolic blood pressure, and heart rate did not differ between diabetic and nondiabetic subjects as assessed by repeated-measures analysis of variance. Because of the theoretical basis for anticipating that diabetes mellitus may provoke important pharmacokinetic and pharmacodynamic alterations, our study provides an important database in clearly demonstrating that the diabetic milieu did not alter the pharmacokinetics or pharmacodynamics of amlodipine.

RCT Entities:   Population Interventions Outcomes