title: Dose dependent effect of diltiazem on the pharmacokinetics of nifedipine.
abstract: The effect of diltiazem pretreatment on the pharmacokinetics of nifedipine were determined in six healthy male volunteers. Placebo or diltiazem (30 mg and 90 mg) was given orally three times daily for 3 days in a double-blind, Latin square method. On the fourth day, a 20-mg nifedipine was given orally 1 hour after the last dose of placebo or diltiazem. The mean elimination half-life of nifedipine prolonged significantly following diltiazem (2.54 hours on placebo vs 3.40 hours on 30 mg diltiazem and 3.47 on 90 mg diltiazem, both P less than .01). The mean AUC of nifedipine increased during diltiazem (1726.6 nmol X hr/ml on placebo vs 3838.0 on 30 mg diltiazem, and 5370.0 on 90 mg diltiazem, both P less than .05, 30 mg vs 90 mg, 0.1 less than P less than .05). The ratio of the AUC of primary metabolite (nitropyridine form) to the AUC of nifedipine was reduced by diltiazem pretreatment in a dose-dependent manner. ICG clearance was not influenced following diltiazem. These results indicate that diltiazem dose-dependently alters the pharmacokinetic profiles of nifedipine. The ICG clearance test showed that the liver blood flow did not decrease during diltiazem therapy, therefore, the reduction in the metabolic clearance of nifedipine might be caused by inhibiting effect of diltiazem on the activity of drug oxidizing enzymes.
authors.affiliation: Department of Clinical Pharmacology, Jichi Medical School, Tochigi-ken, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tateishi
authors.forename: K
authors.initials: K
authors.lastname: Ohashi
authors.forename: T
authors.initials: T
authors.lastname: Sudo
authors.forename: K
authors.initials: K
authors.lastname: Sakamoto
authors.forename: N
authors.initials: N
authors.lastname: Toyosaki
authors.forename: S
authors.initials: S
authors.lastname: Hosoda
authors.forename: T
authors.initials: T
authors.lastname: Toyo-oka
authors.forename: Y
authors.initials: Y
authors.lastname: Kumagai
authors.forename: K
authors.initials: K
authors.lastname: Sugimoto
authors.forename: A
authors.initials: A
authors.lastname: Fujimura
mesh_terms: D000328:Adult; D002849:Chromatography, Gas; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004563:Electrochemistry; D006801:Humans; D007208:Indocyanine Green / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000097:blood / Q000493:pharmacokinetics*; D011725:Pyridines / Q000378:metabolism
chemical_list: D011725:Pyridines; C052728:4-nitropyridine; D004110:Diltiazem; D009543:Nifedipine; D007208:Indocyanine Green