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The Effect of Diltiazem on Hepatic Drug Oxidation Assessed by Antipyrine and Trimethadione
Author(s) -
Ohashi Kyoichi,
Sakamoto Koichi,
Sudo Toshiaki,
Tateishi Tomonori,
Harada Kazuhiro,
Fujimura Akio,
Ebihara Akio,
Tanaka Einosuke
Publication year - 1991
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.1552-4604.1991.tb03685.x
Subject(s) - diltiazem , chemistry , pharmacokinetics , metabolite , pharmacology , volume of distribution , excretion , active metabolite , medicine , endocrinology , calcium , biochemistry , organic chemistry
The effect of pretreatment for 3 days with diltiazem 60 mg three times a day on the pharmacokinetics of 500‐mg antipyrine and 250‐mg trimethadione was studied in six healthy male subjects. Diltiazem decreased the total body clearance from 34.0 ± 8.0 to 28.6 ± 6.1 mL/min (P <.01), and prolonged the elimination half‐life from 12.6 ± 3.0 to 14.3 ± 2.5 hours (P <.01) of antipyrine without any changes in volume of distribution. The cumulative renal excretion (% dose) of antipyrine was significantly increased from 2.23 ± 0.73 to 2.78 ± 0.83% (P <.05). Clearances of production for three major antipyrine metabolites, norantipyrine (4.31 ± 1.64 to 3.50 ± 1.28 mL/min, P <.01), 3‐hydroxymethy‐lantipyrine (4.67 ± 1.63 to 3.82 ± 1.34 mL/min, P <.01) and 4‐hydroxyantipyrine (10.47 ± 3.41 to 8.16 ± 2.82 mL/min, P <.01) were reduced significantly by diltiazem. On the other hand, diltiazem did not produce any significant changes in pharmacokinetic parameters of trimethadione and plasma concentration ratio, oxidative major metabolite of trimethadione to trimethadione itself. These results suggest that other drugs metabolizing the same hepatic oxidative pathways as antipyrine, may be influenced by diltiazem.