J. Azuma et al., EFFECTS OF GRAPEFRUIT JUICE ON THE PHARMACOKINETICS OF THE CALCIUM-CHANNEL BLOCKERS NIFEDIPINE AND NISOLDIPINE, Current therapeutic research, 59(9), 1998, pp. 619-634
Citations number
26
Categorie Soggetti
Pharmacology & Pharmacy","Medicine, Research & Experimental
This study was designed to investigate the effects of marketed grapefr
uit juice (GFJ) on the pharmacokinetics of nifedipine and nisoldipine
and of the time between ingestion of GFJ and drug administration in Ja
panese subjects. Two groups of eight healthy men received single oral
doses of nifedipine 20 mg or nisoldipine 10 mg on four dosing schedule
s: (1) with GFJ; (2) 1 hour after drinking GFJ; (3) 1 hour before drin
king GFJ; and (4) with water alone. GFJ had relatively minor effects o
n nifedipine pharmacokinetics, whereas plasma nisoldipine concentratio
ns were increased by drug administration with or within 1 hour before
or after GFJ ingestion. Nifedipine and nisoldipine were well tolerated
in each dosing schedule, suggesting that no clinically relevant inter
actions occurred. However, it would be wise to avoid drinking GFJ with
in 1 hour before or after taking nisoldipine, because the combination
increases plasma drug concentrations. Inhibition of the metabolism of
dihydropyridines could not be ruled out, because bioflavonoids and fur
anocoumarines were present in the marketed GFJ, The observed differenc
es in the effects of GFJ on the pharmacokinetics of nifedipine and nis
oldipine in this parallel study appear to be attributable to the diffe
rences in their bioavailability.