title: Impairment of the metabolism of dipyrone in asymptomatic carriers of the hepatitis-B virus does not occur in rapid acetylators.
abstract: OBJECTIVE
  We previously found that, compared with healthy subjects. asymptomatic hepatitis-B virus (HBV) carriers displaying slow acetylator phenotype demonstrate a significant prolongation of the elimination half-life of 4-methylaminoantipyrine (MAA) and a decrease in the clearance of formation of 4-aminoantipyrine (AA) and 4-formylaminoantipyrine (FAA). However, the formation of 4-acetylaminoantipyrine (AAA) was unchanged. The present study was designed to examine the effect of the asymptomatic HBV carrier state on the metabolism of dipyrone. as a model drug, in rapid acetylators.
  
  
  METHODS
  The plasma and urine concentrations of the metabolites of dipyrone were measured in eight asymptomatic HBV carriers and eight healthy subjects who had normal liver function tests, all displaying the rapid acetylation phenotype and genotype, after the administration of a 1.0-g oral dose of dipyrone.
  
  
  RESULTS
  The following pharmacokinetic parameters were evaluated: peak plasma concentration, time to peak plasma concentration, elimination rate constant, area under the plasma concentration-time curve (0-->infinity), amount excreted (0-->infinity), renal and non-renal clearances for MAA and the clearances of formation for AA, FAA and AAA. No significant differences were found between the two subject groups.
  
  
  CONCLUSIONS
  The effect of hepatic viral carrier state on drug metabolism may vary according to metabolic pathways and genetic polymorphism.
authors.affiliation: Department of Medicine, Hadassah University Hospital, Jerusalem, Israel. mlevy@md.huji.ac.il
authors.forename: M
authors.initials: M
authors.lastname: Levy
authors.forename: R
authors.initials: R
authors.lastname: Safadi
authors.forename: E
authors.initials: E
authors.lastname: Zylber-Katz
authors.forename: L
authors.initials: L
authors.lastname: Granit
authors.forename: Y
authors.initials: Y
authors.lastname: Caraco
mesh_terms: D000107:Acetylation; D000328:Adult; D000465:Algorithms; D000632:Aminopyrine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D000675:Ampyrone / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002353:Carrier State / Q000097:blood; D004177:Dipyrone / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics* / Q000652:urine; D005260:Female; D006207:Half-Life; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D047069:Pyrazolones
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D047069:Pyrazolones; D000632:Aminopyrine; D000675:Ampyrone; C011256:4-formylaminoantipyrine; D004177:Dipyrone; C010403:N-acetylaminoantipyrine; C008667:noramidopyrine