P-259: Effects of type II diabetes mellitus on the comparative pharmacokinetics and pharmacodynamics of amlodipine in hypertensive patients

• Published in: American journal of hypertension 2001-04, Vol.14 (S1), p.115A-115A
• Main Authors: Preston, Richard A., Chung, Menger, Gaffney, Michael, Alonso, Alberto, Baltodano, Neyton M., Epstein, Murray
• Format: Article
• Language: English
• Subjects: Amlodipine; Hypertension in diabetes mellitus; Pharmacokinetics
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(01)02113-6

Introduction: Recent clinical trials aimed at attenuating complications in diabetes mellitus have generated interest in the impact of drug formulation on altered pharmacokinetics (PK) and pharmacodynamics (PD) in diabetes. This study investigates the PK and PD of amlodipine in hypertensive subjects with and without diabetes mellitus to determine whether the diabetic state alters these parameters. Methods: Two-week placebo wash-out phase, two week titration phase, and two-week maintenance phases. Patients included 18 hypertensive patients with Type II diabetes mellitus and 10 nondiabetic hypertensive patients. Patients were admitted to the University of Miami Division of Clinical Pharmacology Research Center for 24-hour PK and PD studies. AUC, Cmax, and Tmax were analyzed for differences between hypertensive patients with and without diabetes on day 28 when all 28 subjects received amlodipine 5 mg and at day 42 for the 21 subjects who received amlodpine 10mg. The acute PD response to amlodipine was assessed by systolic and diastolic blood pressure changes and by telemetric heart rate monitoring. Results: There were no significant differences for either amlodipine 5 or 10 mg in AUC, Cmax, and Tmax between diabetic and non-diabetic hypertensive subjects. The 24-hour pharmacodynamic effects of amlodipine on systolic blood pressure, diastolic blood pressure, and telemetric heart rate did not differ between diabetic and nondiabetic subjects as assessed by repeated measures analysis of variance. Conclusion: Because of the theoretical basis for anticipating that diabetes mellitus may provoke important pharmacokinetic and pharmacodynamic alterations, our study provides an important data base in clearly demonstrating that the diabetic milieu did not alter the pharmacokinetics or pharmacodynamics of amlodipine. Whether diabetes mellitus alters the PK or PD of other dihydropyridines remains to be studied. (See Table) Amlodipine 5 mg (day 28) DM No DM p-value AUC (hr*ng/ml) 304.1 (165.3) 252.5 (121.2) .40 Cmax (ng/ml) 16.6 (9.4) 13.7 (7.5) .41 Tmax (hr) 8.2 (2.4) 8.6 (5.0) .79 Amlodipine 10 mg (day 42) AUC (hr*ng/ml) 584.0 (244.6) 525.4 (234.0) .59 Cmax (ng/ml) 31.6 (13.2) 27.2 (11.8) .45 Tmax (hr) 7.2 (2.0) 7.8 (4.4) .67