Influence of grape juice and orange juice on the pharmacokinetics and pharmacodynamics of diltiazem in healthy human male subjects

Abstract

The objective was to study the effect of grape juice and orange juice on the pharmacokinetics (PK) and pharmacodynamics (PD) of diltiazem in healthy human volunteers. The study design was open-label, balanced, randomized, 3-period, single-dose and crossover. A group of 12 healthy, adult, male human volunteers received a single oral dose of diltiazem 180 mg extended release capsule on three different occasions: with 200 ml of water, with 200 ml of grape juice and with 200 ml of orange juice in random order. A washout period of 7 days was kept between each study period. Serial blood samples were collected up to 24 h post dose and assayed for diltiazem using a specific and validated HPLC method. Blood pressure (BP) and ECG measurements were done at 0, 1, 2, 3, 4, 6, 8, 10, 12, 16 and 24 h post dose. Analysis of variance was carried out using logarithmic transformations of AUC and Cmax as well as nontransformed tmax. No significant change was observed in heart rate and BP. The median tmax was identical in all three occasions. The 90% CI of the Cmax ratios for orange juice/water were 104.59 - 114.86 and for grape juice/water were 93.91 - 103.13. Similarly, the 90% CI of the AUC0-inf ratios for orange juice and grape juice vs. water were 103.68 - 119.83 and 88.56 - 104.06, respectively. Since these values fall within the bioequivalence criteria of 80 - 120% limits, our study demonstrates absence of interaction of diltiazem with grape juice or orange juice. There is no significant influence of grape juice or orange juice on the pharmacokinetics and pharmacodynamics of diltiazem.