Effects of cytochrome P-450 inducers on the perazine metabolism in a primary culture of human hepatocytes.
The metabolism of perazine in a primary culture of human hepatocytes after treatment of cells with TCDD (a CYP1A1/2 inducer) or rifampicin (mainly a CYP3A4 inducer) were studied in vitro. The concentrations of perazine and its main metabolites (perazine 5-sulfoxide, N-desmethylperazine) formed in hepatocytes were assayed in the extracellular medium using the HPLC method. TCDD and rifampicin induced the formation of perazine 5-sulfoxide, however, such an effect was not observed in the case of N-desmethylperazine. The accumulation of perazine 5-sulfoxide in the extracellular medium was enhanced until up to 4 h by rifampicin, and until up to 8 h byTCDD. After 24 h, perazine and perazine 5-sulfoxide were not detected in the extracellular medium of the inducer-treated cultures, except for perazine 5-sulfoxide in the TCDD-treated cultures The obtained results indicate that CYP1A2 and CYP3A4 are involved in the perazine metabolism via 5-sulfoxidation pathway.
Wójcikowski
Jacek
J
Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. wojcikow@if-pan.krakow.pl
Pichard-Garcia
Lydiane
L
Maurel
Patrick
P
Daniel
Władysława A
WA
D001711:Biotransformation / Q000187:drug effects; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010464:Perazine / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D012293:Rifampin / Q000494:pharmacology*; D013997:Time Factors
D000072317:Polychlorinated Dibenzodioxins; D010464:Perazine; D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D012293:Rifampin