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Dose Dependent Effect of Diltiazem on the Pharmacokinetics of Nifedipine
Author(s) -
Tateishi T.,
Ohashi K.,
Sudo T.,
Sakamoto K.,
Toyosaki N.,
Hosoda S.,
Toyooka T.,
Kumagai Y.,
Sugimoto K.,
Fujimara A.,
Ebihara A.
Publication year - 1989
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1989.tb03267.x
Subject(s) - diltiazem , nifedipine , pharmacokinetics , placebo , pharmacology , medicine , drug interaction , calcium , alternative medicine , pathology
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 < .01). The mean AUC of nifedipine increased during diltiazem (1726.6 nmol × hr/ml on placebo vs 3838.0 on 30 mg diltiazem, and 5370.0 on 90 mg diltiazem, both P < .05, 30 mg vs 90 mg, 0.1 < P < .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.