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Inhibition of desipramine 2‐hydroxylation by quinidine and quinine
Author(s) -
Steiner E,
Dumont E,
Spina E,
Dahlqvist R
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.76
Subject(s) - quinidine , quinine , desipramine , chemistry , excretion , pharmacology , debrisoquine , endocrinology , medicine , metabolism , biochemistry , cyp2d6 , cytochrome p450 , malaria , hippocampus , immunology , antidepressant
Urinary excretion of desipramine (DMI) and 2‐hydroxydesipramine (2‐OH‐DMI) after single oral doses of 25 mg DMI was investigated in seven rapid and three slow debrisoquin hydroxylators, before and after pretreatment with either quinidine or its diastereoisomer quinine. After treatment with 800 mg quinidine daily for 2 days, excretion of 2‐OH‐DMI decreased by 96% in rapid hydroxylators and 68% in slow hydroxylators. After treatment with 750 mg quinine/day for 2 days, excretion of 2‐OH‐DMI in rapid hydroxylators was 54% lower than during the control experiment, whereas in slow hydroxylators no significant changes in the excretion pattern were observed. Unchanged DMI constituted only a minor fraction of recovered drug and no significant changes in its recovery were observed in either phenotypic group after pretreatment with quinidine or quinine. Thus both quinidine and quinine decreased the excretion of 2‐OH‐DMI. At similar doses the effect of quinidine was much stronger than that of quinine, virtually transforming rapid hydroxylators into slow hydroxylators. The mechanism probably involves a stereoselective inhibition of DMI 2‐hydroxylation. Clinical Pharmacology and Therapeutics (1988) 43, 577–581; doi: 10.1038/clpt.1988.76