T.Tanigawa (1,2), T.Morikawa (2). H.To (2), S.Higuchi (2)
(1) Clinical Pharmacology, Bayer Yakuhin,Ltd., Osaka, Japan; (2) Clinical Pharmacokinetics, Kyusyu Univ, Japan
Objectives: Adalat CR® tablet, which has been marketed since 1998 in Japan, is a coat-core tablet of nifedipine, consisting of the “outer coating (coat part)” and the “inner core (core part)” with different release rate. We tried to define the pharmacokinetic model with population approach in order to demonstrate pharmacokinetic characteristics of the unique controlled release formulation of nifedipine.
Methods: Pharmacokinetic modelling was performed in 1314 plasma concentrations from 92 healthy male volunteers, who were administered 20mg once daily of Adalat CR® (Bayer Yakuhin, Ltd.). The pharmacokinetic analyses were performed using nonlinear mixed effect modelling with the NONMEM program version V on the validated Linux server farm environment.
Results: After administration of Adalat CR®, dual absorption phase was observed in plasma concentration – time profile of nifedipine. According to the release characteristics of the drug, a modified 3-compartment model was applied; the 1st compartment for absorption from coat part which has slow release rate of nifedipine, the 2nd compartment for central compartment and the 3rd compartment for absorption from core part which has faster nifedipine release rate with a lag time. By combining of the drug concentration from 1st compartment and 3rd compartment, plasma concentration in central compartment was estimated, which fit well to the observed concentration.
Conclusion: Establishing pharmacokinetic model by applying commonly used non-compartment model is sometimes not easy for controlled release formulation. Therefore population approach, which can evaluate covariate effects and inter- and intra- individual variability, was applied.
Reference: PAGE 14 () Abstr 749 [www.page-meeting.org/?abstract=749]
Poster: poster