title: Autoinduction of the metabolism of phenothiazine neuroleptics in a primary culture of human hepatocytes.
abstract: BACKGROUND
  The metabolism of phenothiazine neuroleptics (promazine, perazine) in a primary culture of human hepatocytes after pretreatment of cells with those neuroleptics was studied.
  
  
  METHODS
  The hepatocytes were pretreated with 25 μM promazine or perazine for 96 h. Then, the cells were incubated for 2, 4, 6, 8 and 24 h in the presence of neuroleptics. At the indicated time points, concentrations of phenothiazines and their metabolites (5-sulfoxides and N-desmethyl derivatives) were measured in the culture medium using HPLC with UV detection.
  
  
  RESULTS
  Pretreatment of the primary culture of human hepatocytes with promazine or perazine resulted in accumulation of their metabolites in the culture medium. Such an effect was not observed in the case of control cultures (not pretreated with neuroleptics).
  
  
  CONCLUSIONS
  The obtained results suggest that the tested phenothiazines may stimulate their own metabolism by inducing CYP1A2, CYP3A4 and CYP2C19 isoforms.
authors: Department of Pharmacokinetics and Drug Metabolism, Institute of Pharmacology, Polish Academy of Science, Smętna 12, PL 31-343 Kraków, Poland. wojcikow@if-pan.krakow.pl
authors: Jacek
authors: J
authors: Wójcikowski
authors: Patrick
authors: P
authors: Maurel
authors: Władysława A
authors: WA
authors: Daniel
mesh_terms: D000368:Aged; D014150:Antipsychotic Agents / Q000378:metabolism* / Q000494:pharmacology; D001711:Biotransformation; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D003640:Dealkylation; D004790:Enzyme Induction; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D007527:Isoenzymes; D010464:Perazine / Q000378:metabolism* / Q000494:pharmacology; D061251:Primary Cell Culture; D011395:Promazine / Q000378:metabolism* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013454:Sulfoxides / Q000378:metabolism; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D007527:Isoenzymes; D013454:Sulfoxides; D010464:Perazine; D003577:Cytochrome P-450 Enzyme System; D011395:Promazine