Tags

Type your tag names separated by a space and hit enter

Asymmetric redox reactions in human liver stereoselective oxidation of optically active dihydrohaloperidols, dihydrobromoperidols and stereospecific reduction of haloperidol and bromoperidol.
Enantiomer. 2000; 5(2):189-95.E

Abstract

The stereoselective oxidation of dihydrohaloperidols (3a, b) and dihydrobromoperidols (4a, b), which are the main metabolites of haloperidol (1) and bromoperidol (2) in humans, respectively, were pharmacokinetically investigated using human liver microsomes and human cytochrome P450(CYP) isoenzymes expressed in the human cell line. The oxidation rates of the (R)-isomers (3a and 4a) in the human liver microsomes were faster than those of the (S)-isomers (3b and 4b), and the R/S enantiomeric ratios of 3 and 4 for intrinsic clearance (Vmax/Km) were 1.40 and 3.10, respectively, showing that stereoselective oxidation occurred in human liver. Concerning the involvement of the CYP isoenzymes in this oxidative pathway, the (R)-isomers (3a and 4a) were catalyzed by both CYP3A4 and CYP2D6, however, the (S)-isomers (3b and 4b) were catalyzed only by CYP3A4.

Authors+Show Affiliations

Takeshita M
Department of Pharmaceutical Sciences, Tohoku Pharmaceutical University, Sendai, Japan. mtake@tohoku-pharm.ac.jp
Miura M
No affiliation info available
Ohkubo T
No affiliation info available
Sugawara K
No affiliation info available

MeSH

Chromatography, High Pressure LiquidCytochrome P-450 CYP2D6Cytochrome P-450 CYP3ACytochrome P-450 Enzyme SystemCytosolHaloperidolHumansMicrosomes, LiverMixed Function OxygenasesOxidation-ReductionStereoisomerism

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10857058

Citation

Takeshita, M, et al. "Asymmetric Redox Reactions in Human Liver Stereoselective Oxidation of Optically Active Dihydrohaloperidols, Dihydrobromoperidols and Stereospecific Reduction of Haloperidol and Bromoperidol." Enantiomer, vol. 5, no. 2, 2000, pp. 189-95.
Takeshita M, Miura M, Ohkubo T, et al. Asymmetric redox reactions in human liver stereoselective oxidation of optically active dihydrohaloperidols, dihydrobromoperidols and stereospecific reduction of haloperidol and bromoperidol. Enantiomer. 2000;5(2):189-95.
Takeshita, M., Miura, M., Ohkubo, T., & Sugawara, K. (2000). Asymmetric redox reactions in human liver stereoselective oxidation of optically active dihydrohaloperidols, dihydrobromoperidols and stereospecific reduction of haloperidol and bromoperidol. Enantiomer, 5(2), 189-95.
Takeshita M, et al. Asymmetric Redox Reactions in Human Liver Stereoselective Oxidation of Optically Active Dihydrohaloperidols, Dihydrobromoperidols and Stereospecific Reduction of Haloperidol and Bromoperidol. Enantiomer. 2000;5(2):189-95. PubMed PMID: 10857058.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Asymmetric redox reactions in human liver stereoselective oxidation of optically active dihydrohaloperidols, dihydrobromoperidols and stereospecific reduction of haloperidol and bromoperidol. AU - Takeshita,M, AU - Miura,M, AU - Ohkubo,T, AU - Sugawara,K, PY - 2000/6/17/pubmed PY - 2000/7/8/medline PY - 2000/6/17/entrez SP - 189 EP - 95 JF - Enantiomer JO - Enantiomer VL - 5 IS - 2 N2 - The stereoselective oxidation of dihydrohaloperidols (3a, b) and dihydrobromoperidols (4a, b), which are the main metabolites of haloperidol (1) and bromoperidol (2) in humans, respectively, were pharmacokinetically investigated using human liver microsomes and human cytochrome P450(CYP) isoenzymes expressed in the human cell line. The oxidation rates of the (R)-isomers (3a and 4a) in the human liver microsomes were faster than those of the (S)-isomers (3b and 4b), and the R/S enantiomeric ratios of 3 and 4 for intrinsic clearance (Vmax/Km) were 1.40 and 3.10, respectively, showing that stereoselective oxidation occurred in human liver. Concerning the involvement of the CYP isoenzymes in this oxidative pathway, the (R)-isomers (3a and 4a) were catalyzed by both CYP3A4 and CYP2D6, however, the (S)-isomers (3b and 4b) were catalyzed only by CYP3A4. SN - 1024-2430 UR - https://www.unboundmedicine.com/medline/citation/10857058/Asymmetric_redox_reactions_in_human_liver_stereoselective_oxidation_of_optically_active_dihydrohaloperidols_dihydrobromoperidols_and_stereospecific_reduction_of_haloperidol_and_bromoperidol_ DB - PRIME DP - Unbound Medicine ER -