Formulation dependent pharmacokinetics--does the dosage form matter for nifedipine?
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.
Toal
Corey B
CB
Department of Pharmacology, University of Toronto and Bayer Inc., Toronto, Ontario, Canada. corey.toal.b@bayer.com
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D006801:Humans; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D002121:Calcium Channel Blockers; D002214:Capsules; D003692:Delayed-Action Preparations; D009543:Nifedipine