H. Takanaga et al., Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects, CLIN PHARM, 67(3), 2000, pp. 201-214
A clinical study was performed in eight healthy volunteers to investigate t
he effect of various timing of grapefruit juice intake on nisoldipine pharm
acokinetics and pharmacodynamics, and to validate our pharmacokinetic model
. The subjects were given 10 mg oral nisoldipine with water (control), or 5
mg oral nisoldipine with 200 mt grapefruit juice (G0) or with water at 14
(G14), 38 (G38), 72 (G72) or 96 hours (G96) after a 7-day period of thrice-
daily intake of grapefruit juice, Grapefruit juice ingestion did not affect
heart rate or the effect ar ea during the first 8 hours of heart rate afte
r nisoldipine administration, although significant decreases of systolic an
d diastolic blood pressure were caused in G0 by coadministration of grapefr
uit juice with nisoldipine, Headaches were reported by 3, 2, and 1 persons
in G0, G14, and G38, respectively, but no subjects in G72 and G96 reported
headaches. Compared with the control group, the maximum plasma concentratio
n of nisoldipine was significantly increased after grapefruit juice intake
in G0 and G14, and the plasma concentration was significantly increased at
each time in G0 to G72, Therefore the effect of grapefruit juice decreased
time dependently and lasted for at least 3 days after intake. Furthermore,
our model have predicted values in good agreement with the observed values,
It is therefore necessary to withhold grapefruit juice for at least 3 days
before administration of the drug to prevent grapefruit juice-nisoldipine
interaction.