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Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase).
Br J Clin Pharmacol. 1991 Jun; 31(6):655-60.BJ

Abstract

1. The conversion of haloperidol (HAL) to reduced haloperidol (RHAL) and then back to HAL has been established in vivo and observed in psychiatric patients. The reduction of HAL to RHAL is known to be catalysed by a ketone reductase, while the nature of oxidation back to HAL is the subject of the present study. 2. We examined the in vitro oxidation of RHAL to HAL in human livers. The activity was microsomal and evidence is presented to suggest that the sparteine/debrisoquine metabolizing isoenzyme P450IID6 contributes to this oxidation. 3. Reciprocal inhibition studies between RHAL and sparteine, a specific substrate for cytochrome P450IID6, indicated that both compounds compete for the same binding site. Quinidine, the most specific inhibitor for this cytochrome P450 potently inhibited the oxidative conversion of reduced haloperidol to haloperidol. A significant correlation (rs = 0.62, P less than 0.01) was found between RHAL oxidation and sparteine oxidation in a study involving 17 human liver samples.

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Authors+Show Affiliations

Tyndale RF
Department of Pharmacology, University of Toronto, Canada.
Kalow W
No affiliation info available
Inaba T
No affiliation info available

MeSH

Cytochrome P-450 CYP2D6Cytochrome P-450 Enzyme InhibitorsCytochrome P-450 Enzyme SystemHaloperidolHumansIn Vitro TechniquesMicrosomes, LiverMixed Function OxygenasesOxidation-ReductionQuinidineQuinine

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1867960

Citation

Tyndale, R F., et al. "Oxidation of Reduced Haloperidol to Haloperidol: Involvement of Human P450IID6 (sparteine/debrisoquine Monooxygenase)." British Journal of Clinical Pharmacology, vol. 31, no. 6, 1991, pp. 655-60.
Tyndale RF, Kalow W, Inaba T. Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase). Br J Clin Pharmacol. 1991;31(6):655-60.
Tyndale, R. F., Kalow, W., & Inaba, T. (1991). Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase). British Journal of Clinical Pharmacology, 31(6), 655-60.
Tyndale RF, Kalow W, Inaba T. Oxidation of Reduced Haloperidol to Haloperidol: Involvement of Human P450IID6 (sparteine/debrisoquine Monooxygenase). Br J Clin Pharmacol. 1991;31(6):655-60. PubMed PMID: 1867960.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidation of reduced haloperidol to haloperidol: involvement of human P450IID6 (sparteine/debrisoquine monooxygenase). AU - Tyndale,R F, AU - Kalow,W, AU - Inaba,T, PY - 1991/6/1/pubmed PY - 1991/6/1/medline PY - 1991/6/1/entrez SP - 655 EP - 60 JF - British journal of clinical pharmacology JO - Br J Clin Pharmacol VL - 31 IS - 6 N2 - 1. The conversion of haloperidol (HAL) to reduced haloperidol (RHAL) and then back to HAL has been established in vivo and observed in psychiatric patients. The reduction of HAL to RHAL is known to be catalysed by a ketone reductase, while the nature of oxidation back to HAL is the subject of the present study. 2. We examined the in vitro oxidation of RHAL to HAL in human livers. The activity was microsomal and evidence is presented to suggest that the sparteine/debrisoquine metabolizing isoenzyme P450IID6 contributes to this oxidation. 3. Reciprocal inhibition studies between RHAL and sparteine, a specific substrate for cytochrome P450IID6, indicated that both compounds compete for the same binding site. Quinidine, the most specific inhibitor for this cytochrome P450 potently inhibited the oxidative conversion of reduced haloperidol to haloperidol. A significant correlation (rs = 0.62, P less than 0.01) was found between RHAL oxidation and sparteine oxidation in a study involving 17 human liver samples. SN - 0306-5251 UR - https://www.unboundmedicine.com/medline/citation/1867960/Oxidation_of_reduced_haloperidol_to_haloperidol:_involvement_of_human_P450IID6__sparteine/debrisoquine_monooxygenase__ DB - PRIME DP - Unbound Medicine ER -