title: Pharmacokinetics of mycophenolic acid in kidney transplant patients receiving sirolimus versus cyclosporine.
abstract: BACKGROUND
  Mycophenolic acid (MPA) pharmacokinetics exhibit large variability in transplant recipients and may be altered due to concurrent immunosuppressants. Little is known about the influence of sirolimus (SRL) on MPA pharmacokinetics in kidney transplant patients.
  
  
  METHODS
  We studied the areas under concentration-time curves (AUC) for MPA in 15 patients receiving immunosuppression combining SRL with mycophenolate mofetil (MMF). The pharmacokinetic measurements were performed in all patients using three MMF dosing regimens (0.5 g twice a day, 0.75 g twice a day, 1 g twice a day). Similar blood AUC profiles were also sampled from 12 patients treated with a fixed dose of MMF 1 g twice a day and cyclosporine (CsA). MPA was measured using HPLC; the AUC0-12 of MPA was determined by the trapezoidal method using four sampling time points: C0, C1, C3, C5.
  
  
  RESULTS
  While patients on SRL were receiving 0.75 g MMF twice a day, mean AUC0-12 and C0 values of MPA were comparable to those of patients receiving CsA and 1 g MMF twice a day (54.1 +/- 17.6 and 3 +/- 1.87 vs 51.7 +/- 16.7 mg.h/L and 2.76 +/- 1.57 mg/L, respectively). On the other hand, 0.5 g MMF twice a day with SRL therapy resulted in AUC0-12 and C0 values of MPA of 32.3 +/- 12.6 mg.h/L and 2.32 +/- 1.72 mg/L, respectively, whereas, 1 g MMF twice a day with SRL resulted in AUC0-12 and C0 values of MPA of 70.9 +/- 19.3 mg.h/L and 4.7 +/- 2.44 mg/L, respectively.
  
  
  CONCLUSIONS
  These findings demonstrate that MPA exposure in the presence of SRL is higher than that with CsA. It appears that the MMF dose should be reduced to 0.75 g twice a day in patients receiving SRL to obtain AUC0-12 of MPA levels comparable to that in patients treated with CsA and MMF 1 g twice a day.
authors.affiliation: Department of Nephrology and Renal Transplantation, Caen University Hospital, Caen, France. elhaggan-w@chu-caen.fr
authors.forename: W
authors.initials: W
authors.lastname: El Haggan
authors.forename: M
authors.initials: M
authors.lastname: Ficheux
authors.forename: D
authors.initials: D
authors.lastname: Debruyne
authors.forename: N
authors.initials: N
authors.lastname: Rognant
authors.forename: T
authors.initials: T
authors.lastname: Lobbedez
authors.forename: C
authors.initials: C
authors.lastname: Allard
authors.forename: A
authors.initials: A
authors.lastname: Coquerel
authors.forename: J P
authors.initials: JP
authors.lastname: Ryckelynck
authors.forename: B
authors.initials: B
authors.lastname: Hurault de Ligny
mesh_terms: D019540:Area Under Curve; D001835:Body Weight; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D020123:Sirolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D009173:Mycophenolic Acid; D020123:Sirolimus