title: Simultaneous estimation of cyclosporin and mycophenolic acid areas under the curve in stable renal transplant patients using a limited sampling strategy.
abstract: OBJECTIVE
  Area under the curve (AUC)-based monitoring of cyclosporin (CsA) could help to optimise therapeutic drug monitoring in certain transplant patients in addition to trough concentration monitoring. It is the method of choice for mycophenolic acid (MPA). The objective of this study was to develop a limited sampling strategy for simultaneous estimation of CsA and MPA AUCs in long-term renal transplant patients.
  
  
  METHODS
  Twenty kidney transplant patients treated with CsA and mycophenolate mofetil were included in a pharmacokinetic study more than 6 months after transplantation. Multilinear regression analyses were performed to develop a model enabling the estimation of both drugs' AUCs using a limited number of samples. Dose-normalised data were used throughout the analysis.
  
  
  RESULTS
  Trough concentrations of MPA were poorly correlated with AUC, either used alone (r2 = 0.232) or together with other concentrations. Several models for CsA AUC estimation met the predefined criteria (r2>0.9, P<0.05). The AUC of MPA was best estimated by a three-concentration model (AUC=0.58 C20 min+ 0.97 C1 h + 6.64 C3 h + 3.48; r2 = 0.946). These sampling times also applied to CsA AUC (AUC = 1.17 C20 min + 0.68 C1 h + 5.36 C3 h + 4.24; r = 0.985). AUCs estimated using these models in our patients using the jack-knife procedure were found to be precise and unbiased as compared with reference trapezoidal AUCs.
  
  
  CONCLUSIONS
  We were able to develop a multilinear regression model for simultaneous estimation of both CsA and MPA AUCs using only three blood samples taken up to 3 h post-dosing.
authors.affiliation: Department of Pharmacology, Tours University Hospital, France. leguellec@med.univ-tours.fr
authors.forename: Chantal
authors.initials: C
authors.lastname: Le Guellec
authors.forename: Matthias
authors.initials: M
authors.lastname: Büchler
authors.forename: Bruno
authors.initials: B
authors.lastname: Giraudeau
authors.forename: Yannick
authors.initials: Y
authors.lastname: Le Meur
authors.forename: Jean-Emmanuel
authors.initials: JE
authors.lastname: Gakoué
authors.forename: Yvon
authors.initials: Y
authors.lastname: Lebranchu
authors.forename: Pierre
authors.initials: P
authors.lastname: Marquet
authors.forename: Gilles
authors.initials: G
authors.lastname: Paintaud
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D012044:Regression Analysis
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid