Determination of bufuralol and its major metabolites in plasma by high-performance liquid chromatography

Haefelfinger, P.

doi:10.1016/s0378-4347(00)84318-2

Cited by 18 publications

(4 citation statements)

References 3 publications

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“…In immunoinhibition studies, the antibody (immunoglobulin G fraction) was incubated with microsomes for 20 min at 23 °C before the addition of other components. Assay procedures for the estimation of rates of nifedipine oxidation (28), bufuralol l'-hydroxylation (31), phenacetin O-deethylation (32), tolbutamide methyl hydroxylation (33), mephenytoin 4'-hydroxylation and N-demethylation (25), coumarin 7-hydroxylation (34)(35)(36), N,Af-dimethylnitrosamine Ndemethylation (11,37), and chlorzoxazone 6-hydroxylation (38) are described elsewhere. Some details of assays related to P-450 IIEl activity are presented in Table I.…”

Section: Methodsmentioning

confidence: 99%

Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects

Guengerich

Kim²,

Iwasaki³

1991

Chem. Res. Toxicol.

1,121

558

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The role of human cytochrome P-450 IIE1 (P-450 IIE1) in the oxidation of a number of suspect carcinogens was examined by using a variety of approaches, including (1) selective inhibition of catalytic activity in human liver microsomes by diethyldithiocarbamate, which was found to be a selective mechanism-based inactivator of P-450 IIE1, (2) correlation of rates of different catalytic activities with each other and with chlorzoxazone 6-hydroxylation, an indicator of P-450 IIE1, in human liver microsomes, (3) demonstration of catalytic activity in reconstituted systems containing purified human P-450 IIE1, and (4) immunoinhibition of catalytic activity in human liver microsomes with rabbit anti-human P-450 IIE1. The results collectively indicate that P-450 IIE1 is a major catalyst of the oxidation of benzene, styrene, CCl4, CHCl3, CH2Cl2, CH3Cl, CH3CCl3, 1,2-dichloropropane, ethylene dichloride, ethylene dibromide, vinyl chloride, vinyl bromide, acrylonitrile, vinyl carbamate, ethyl carbamate, and trichloroethylene. Levels of P-450 IIE1 can vary considerably among individual humans--the availability of chlorzoxazone as a noninvasive probe of human P-450 IIE1 and of disulfiram (oxidized diethyldithiocarbamate) as an inhibitor may facilitate discernment of the in vivo significance of human P-450 IIE1 as a factor in the bioactivation and detoxication of these cancer suspects. Further, many investigations with diethyldithiocarbamate, disulfiram, and ethanol in humans and experimental animals may be interpreted in light of mechanisms involving P-450 IIE1.

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Section: Methodsmentioning

confidence: 99%

Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects

Guengerich

Kim²,

Iwasaki³

1991

Chem. Res. Toxicol.

1,121

558

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“…Previously described assay procedures were used for the estimation of rates of 7-ethoxyresorufin O-dealkylation (27-29), coumarin 7-hydroxylation (30)(31)(32), mephenytoin 4'-hydroxylation (33), bufuralol l'-hydroxylation (34), chlorzoxazone 6-hydroxylation (35), and nifedipine oxidation (36).…”

Section: Methodsmentioning

confidence: 99%

“…Since the use of P450 and FMO inhibitors suggested that P450 enzymes mediate the majority of oxidation of IV-Ac-PCBC to the corresponding sulfoxide diastereomers, subsequent studies were directed to the elucidation of the P450 enzyme(s) involved. For this purpose, liver microsomes from 13 individuals of both sexes were used to correlate IV-Ac-PCBC SO formation with catalytic activities known to be associated with a specific P450 isoenzyme, i.e., P450s 1A2, 2A6, 2C19, 2D6, 2E1, and 3A4 (27)(28)(29)(30)(31)(32)(33)(34)(35)(36). The results obtained indicated that only one P450 enzyme, P450 3A4, correlated with IV-Ac-PCBC oxidation (Table 2), as judged from the correlation coefficient determined (0.83).…”

Section: Correlation Of Sulfoxide Formation Rates Inmentioning

confidence: 99%

The Sulfoxidation of the Hexachlorobutadiene Metabolite N-Acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine Is Catalyzed by Human Cytochrome P450 3A Enzymes

Werner¹,

Guo²,

Birner³

et al. 1995

Chem. Res. Toxicol.

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The sulfoxidation of the mercapturic acid N-acetyl-S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine (N-Ac-PCBC), a urinary metabolite of the renal toxin hexachlorobutadiene (HCBD), was studied in human liver microsomes and with purified cDNA expressed human liver cytochrome P450 (P450) enzymes. N-Acetyl-S-(1,2,3,4,4-pentachlorobuta-1,3-dienyl)-L-cysteine sulfoxide (N-Ac-PCBC SO) is a major urinary metabolite of HCBD in male rats; only liver microsomes from male rats catalyze the sulfoxidation of N-Ac-PCBC. Our results presented here show that human liver microsomes from both male and female donors are capable of oxidizing N-Ac-PCBC to the corresponding sulfoxide diastereomers. The correlation of N-Ac-PCBC sulfoxidation with the rates of oxidation of P450 enzyme specific substrates suggests that only P450 3A enzymes oxidize N-Ac-PCBC. Moreover, only gestodene and troleandomycin, two selective inhibitors for P450 of the 3A family, significantly reduced the rates of N-Ac-PCBC sulfoxidation. No reduction in sulfoxidation rates was observed with inhibitors for other P450 enzymes, i.e., diethyldithiocarbamate, 4-methylpyrazole, 7,8-benzoflavone, or sulfaphenazole. Incubations of N-Ac-PCBC with purified and reconstituted recombinant P450s 1A2, 2E1, 3A4, and 3A5 resulted in sulfoxide formation only with P450s 3A4 and 3A5. In summary, these results indicate that P450 from the 3A family may sulfoxidize N-Ac-PCBC. Since these P450 enzymes account for a major fraction of the P450 in human liver and are also present in human kidney, the sulfoxidation reaction may also be expected to occur in humans exposed to HCBD.

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“…The protocol was approved by the Institution Ethical Committee and informed consent was obtained from each subject. Bufuralol and l'-hydroxybufuralol plasma concentrations were measured using a highperformance liquid chromatographic method (Haefelfinger, 1980). Figure 1 shows plasma concentrations of bufuralol and 1'-hydroxybufuralol in the family of our subject (F.K.)…”

Section: Defective Hydroxylation Of Bufuralol Associated With Side-efmentioning

confidence: 99%

Defective hydroxylation of bufuralol associated with side‐effects of the drug in poor metabolisers [letter]

Dayer¹,

Kubli²,

Küpfer³

et al. 1982

Brit J Clinical Pharma

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Determination of bufuralol and its major metabolites in plasma by high-performance liquid chromatography

Cited by 18 publications

References 3 publications

Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects

Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects

The Sulfoxidation of the Hexachlorobutadiene Metabolite N-Acetyl-S-(1,2,3,4,4-pentachlorobutadienyl)-L-cysteine Is Catalyzed by Human Cytochrome P450 3A Enzymes

Defective hydroxylation of bufuralol associated with side‐effects of the drug in poor metabolisers [letter]

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