Interaction of citrus juices with pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy subjects

Objectives: The study was conducted to investigate whether oral co-administ ration with citrus juices significantly affects the pharmacokinetics and/or pharmacodynamics of pranidipine, a new 1,4-dihydropyridine calcium antagon ist, in healthy male subjects. Grapefruit juice and orange juice, which wer e both commercially available, were used in this study. Methods: Sixteen healthy male Japanese subjects participated in this study and were divided into two groups for grapefruit juice and orange juice trea tment. The study followed an open-labelled crossover design, comparing the effects of a single oral dose of 2 mg pranidipine taken together with 250 m i citrus juice or 250 mi water. Serum pharmacokinetics of pranidipine, adve rse reactions, blood pressure, heart rate, 12-lead EGG, haematology, clinic al chemistry and urinalysis were measured throughout the study. Results: For grapefruit juice, mean C-max and AUC(0-24 h) were significantl y higher than those of water (P = 0.0003 and 0.0005, respectively, ANOVA) w ith the ratios of log transformed values being 1.50 and 1.74, respectively. There were no differences in t(max) and t(1/2) between the juice and water treatments. A significant increase in heart rate (P = 0.0240, ANOVA with r epeated measurements) was observed in the juice treatment whereas there wer e no significant differences in systolic and diastolic blood pressure betwe en the two treatments. For orange juice, a small decrease in mean C-max was observed compared with water (P = 0.0218, ANOVA) with the ratio being 0.86 , but there was no significant difference in AUC(0-24 h) between the two tr eatments. No marked differences were observed in t(max) and t(1/2). Oral pr anidipine administration with orange juice did not affect heart rate, systo lic and diastolic blood pressures of other parameters for safety evaluation . Conclusions: Oral co-administration with grapefruit juice and pranidipine w as associated with increased bioavailability and changed the pharmacodynami cs of pranidipine, particularly with regard to heart rate. Orange juice int ake with pranidipine did not markedly affect the pharmacokinetics and no cl inically significant changes were observed in the pharmacodynamics and safe ty evaluation.