Reproducibility of nifedipine absorption from GITS tablets: comparison of single-dose pharmacokinetics using 10, 20, 40 and 60 mg nifedipine.
OBJECTIVE
To examine the reproducibility of nifedipine absorption from gastrointestinal therapeutic system (GITS) tablets by comparing the single-dose pharmacokinetic profiles of 4 different dosages administered orally.


METHODS
Twelve healthy male volunteers, aged between 22 and 29 years were enrolled in the open, 4-way, dose escalation study with single oral doses of 10, 20, 40 and 60 mg (two 30 mg) nifedipine GITS tablets. Each administration was separated by a 1-week washout period. Coefficients of variation (CV) of dose-corrected area under the concentration-time curve (AUC) and peak plasma drug concentrations (Cmax) were calculated from the pharmacokinetic profiles.


RESULTS
Mean AUC and mean Cmax were dose-proportional from 10 to 60 mg. Although the CV of 4 mean dose-corrected AUC and Cmax were 5.5% and 17.5%, respectively, CV of dose-corrected AUC and Cmax in each subject varied from 5.1 to 37.4% (mean 11.0%) and from 14.1% to 46.4% (mean 25.8%), respectively.


CONCLUSIONS
Whereas mean plasma nifedipine concentration remained markedly stable over a 16- to 24-hour interval and mean dose-corrected AUC showed good reproducibility with nifedipine GITS, the CV of dose-corrected AUC of the nifedipine GITS tablets in each subject showed large variability.
Tateishi
T
T
Department of Clinical Pharmacology, Hirosaki University School of Medicine, Hirosaki, Aomori, Japan. tateishi@cc.hirosaki-u.ac.jp
Okumura
K
K
Orii
Y
Y
Tanaka
T
T
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007564:Japan; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D013608:Tablets, Enteric-Coated; D013997:Time Factors
D013608:Tablets, Enteric-Coated; D009543:Nifedipine