Formulation dependent pharmacokinetics--does the dosage form matter for nifedipine?

• Published in: Journal of cardiovascular pharmacology Vol. 44; no. 1; p. 82
• Main Author: Toal, Corey B
• Format: Journal Article
• Language: English
• Published: United States 01.07.2004
• Subjects: Administration, Oral; Adult; Area Under Curve; Blood Pressure - drug effects; Calcium Channel Blockers - administration & dosage; Calcium Channel Blockers - blood; Calcium Channel Blockers - pharmacokinetics; Capsules; Chemistry, Pharmaceutical; Cross-Over Studies; Delayed-Action Preparations; Humans; Male; Middle Aged; Nifedipine - administration & dosage; Nifedipine - blood; Nifedipine - pharmacokinetics
• ISSN: 0160-2446
• DOI: 10.1097/00005344-200407000-00011

This was an open-label, randomized, 3-way crossover study that compared in 25 healthy male subjects, the pharmacokinetics of a single 60-mg dose of nifedipine GITS tablet versus (1) 20-mg doses of nifedipine prolonged action tablets given q12h for a total of two doses and (2) 2 x 10 mg doses of nifedipine capsules given q8h for a total of three doses. Following capsule administration, there was a rapid rise in plasma concentration of drug achieving a peak concentration of 196(35) ng/mL (mean and coefficient of variation) within 0.7 (105) hours and an AUC(infinity) of 973(39) ng.hr/mL. After nifedipine PA there was also a rapid rise in plasma concentration of drug achieving a Cmax of 85.5 (36) ng/mL with a tmax of 1.7(58) hours and an AUC(infinity) of 879(46) ng.hr/mL. For the nifedipine GITS formulation, there was a lag in the plasma concentration time profile for approximately 2 to 3 hours, then it rose gradually achieving a Cmax of of 686(54) 30.5(63) ng/mL with a tmax of 15.0(50) hours and an AUC(infinity) ng.hr/mL. The AUC(infinity) and Cmax were significantly (P = 0.0001) greater in the capsule and PA formulations than for the GITS; however, the tmax for the GITS formulation was significantly (P = 0.001) longer than for the other formulations. This study suggests marked formulation-dependent pharmacokinetics, which may have important clinical implications.