title: The effect of short-term dipyrone administration on cyclosporin pharmacokinetics.
abstract: BACKGROUND
  A large number of drugs have been shown to affect the metabolism of cyclosporin A (CSA) and, since cyclosporin is characterized by a narrow therapeutic range, the consequences of such drug interactions may often be of clinical importance.
  
  
  OBJECTIVE
  To evaluate the effect of short-term administration of dipyrone on steady state CSA pharmacokinetics.
  
  
  METHODS
  Six kidney- and two heart-transplanted patients on chronic CSA therapy participated in this study, which consisted of two 4-day study periods separated by 3-week washout periods. The patients received, in addition to their usual drugs, dipyrone 500 mg or placebo t.i.d., as identical-looking tablets, and the order of administration was randomized. CSA concentrations were measured in whole blood by means of radio-immunoassay (CYCLO-Trac SP) daily during the study periods and periodically over 24 h on the fourth study day.
  
  
  RESULTS
  CSA concentrations over time were reduced after dipyrone (ANOVA, P < 0.01), but statistical significance was noted only at 2, 4, 5 and 10 h after drug intake (P < 0.05). Peak CSA concentration was not altered by dipyrone, but the time required to reach maximal concentration was longer with dipyrone treatment than with the placebo (3.8 +/- 2.6 h vs 2.1 +/- 0.6 h, P < 0.05). No consistent changes were noted for CSA trough level, elimination half-life and area under the concentration-time curve from 0 h to 12 h. Separate analysis of the kidney transplanted patients yielded similar results.
  
  
  CONCLUSIONS
  Short-term administration of dipyrone is associated with a mild decrease in CSA blood concentration, which is most prominent in the first few hours after drug intake. In practice, no dose adjustment of CSA seems to be indicated during a short course of dipyrone treatment.
authors.affiliation: Division of Medicine, Clinical Pharmacology Unit, Hadassah University Hospital, Jerusalem, Israel. caraco@hadassah.org.il
authors.forename: Y
authors.initials: Y
authors.lastname: Caraco
authors.forename: E
authors.initials: E
authors.lastname: Zylber-Katz
authors.forename: M
authors.initials: M
authors.lastname: Fridlander
authors.forename: D
authors.initials: D
authors.lastname: Admon
authors.forename: M
authors.initials: M
authors.lastname: Levy
mesh_terms: D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D018592:Cross-Over Studies; D016572:Cyclosporine / Q000493:pharmacokinetics*; D004177:Dipyrone / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D004177:Dipyrone; D016572:Cyclosporine