INFLUENCE OF GRAPEFRUIT JUICE ON THE PHARMACOKINETICS OF A SLOW-RELEASE NIFEDIPINE FORMULATION

The objective of this study was to investigate in a twoway randomized crossover whether repeated uptake of grapefruit juice (200 ml at 0, 2, 4, 8 and 12 h enhances bioavailability of a nifedipine (1) slow relea se formulation (20 mg) in ten healthy volunteers. Grapefruit juice inc reased the AUC and c(max) of 1 statistically significantly by 103 (SD 73, range 48 to 265)% and 94 (SD 83, range -23 to 259)%, respectively. AUC of dehydronifedipine (2) was also higher during grapefruit phase, but to a lesser extent (mean increase 66, SD 106, range - 30 to 236)% . Half lives of neither 1 nor 2 were altered by grapefruit juice. Beca use 2/1 - ratio was not lowered by grapefruit juice in comparison to c ontrol, a selective inhibition of cytochrome P450 3A based on the pres ented in vivo data is not very likely. In the light of other reports c oncerning grapefruit juice induced increase in bioavailability our dat a contradict the assumption of a selective inhibition of only one cyto chrome P450 subfamily. The observed effect could be clinically signifi cant, especially if other factors affecting the elimination of 1 occur .