Pharmacokinetic profile of BAY a 1040 GITS, a nifedipine once-a-day dosage form based on osmotic pump configuration

Abstract

Pharmacokinetic profile and safety of BAY a 1040 GITS (gastrointestinal therapeutic system), a nifedipine once-a-day dosage form based on push-pull osmotic pump configuration, were investigated in Japanese healthy volunteers in single-dose and multiple-dose trials. The single dose trial was conducted in an open, randomized, 4-way crossover method, where 30 mg, and 40 mg nifedipine GITS tablets and 40 mg marketed nifedipine coat-core tablet (Adalat CR®) were given after overnight fasting and 40 mg GITS was given with high-fat breakfast. The multiple-dose trial was an open, randomized, 2-way crossover trial using 40 mg GITS and 40 mg CR tablets for 7 days. In the plasma nifedipine concentration profile, Cmax of 40 mg GITS was significantly lower than that of 40 mg CR, although AUC of 40 mg GITS was similar to that of 40 mg CR in the single-dose trial. When GITS was administered with high-fat breakfast, Cmax was increased by 28%. In the multiple-dose trial, Cmax of GITS was 43.2% lower than that of CR 40 mg, and Cmin was 47.8% higher. Results of both studies indicated that GITS has preferable controlled release properties in the once-a-day dosage form as well as Adalat CR. GITS showed lower intra-day fluctuation in the plasma concentration profile, compared to Adalat CR. However, no major difference was observed in the safety profile or blood pressure/pulse rate profiles between these two once-a-day dosage forms of nifedipine.