title: Effect of clofibrate on the chiral inversion of ibuprofen in healthy volunteers.
abstract: OBJECTIVE
  To determine the influence of the hypolipidemic drug clofibrate on the stereoselective metabolism of ibuprofen in humans.
  
  
  METHODS
  Healthy male subjects (n = 12) ingested a dose of 400 mg pseudoracemic ibuprofen (200 mg R-ibuprofen, 160 mg S-ibuprofen, and 40 mg 13C-S-ibuprofen) on two occasions after either pretreatment with clofibrate (2 gm/day over 1 week) or no pretreatment in a randomized order.
  
  
  RESULTS
  When subjects were pretreated with clofibrate, clearances of R-ibuprofen and 13C-S-ibuprofen increased significantly from 55.0 and 66.4 ml/min to 186.2 and 106.7 ml/min (p < 0.01), respectively. This increase was similarly reflected in the clearance by inversion of R-ibuprofen (control, 36.0 ml/min; treated, 118.8 ml/min; p < 0.01), as well as in the clearance by noninversion (control, 19.0 ml/min; treated, 67.4 ml/min; p < 0.01). Unbound clearance values significantly increased for R-ibuprofen (control, 19.5 L/min; treated, 38.7 L/min) but not for 13C-S-ibuprofen (11.8 versus 10.6 L/min, respectively). The fractional inversion of ibuprofen calculated from the urinary metabolite data was increased after clofibrate pretreatment (clofibrate group, 66.4%; control, 53.5%; p < 0.01). However, this was not evident when fractional inversion was calculated from the plasma concentration-time data for the unmetabolized drug.
  
  
  CONCLUSIONS
  Clofibrate altered the stereoselective disposition of ibuprofen in healthy volunteers by increased formation of R-ibuprofenoyl-coenzyme A rather than by an effect on oxidative metabolism of ibuprofen. This interaction has potential therapeutic implications.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Scheuerer
authors.forename: S D
authors.initials: SD
authors.lastname: Hall
authors.forename: K M
authors.initials: KM
authors.lastname: Williams
authors.forename: G
authors.initials: G
authors.lastname: Geisslinger
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002994:Clofibrate / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D006801:Humans; D000960:Hypolipidemic Agents / Q000097:blood / Q000494:pharmacology* / Q000652:urine; D007052:Ibuprofen / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D008297:Male; D012016:Reference Values; D013237:Stereoisomerism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000960:Hypolipidemic Agents; D002994:Clofibrate; D007052:Ibuprofen