title: Evalutation of mycophenolic acid systemic exposure by limited sampling strategy in kidney transplant recipients receiving enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine.
abstract: BACKGROUND
  Enteric-coated mycophenolate sodium (EC-MPS) and mycophenolate mofetil (MMF) are prodrugs of mycophenolic acid (MPA). Although many patients still receive MMF as an inosine monophosphate dehydrogenase inhibitor, EC-MPS could be considered a reliable alternative to MMF in the immunosuppressive protocols of kidney transplant recipients. MPA shows high pharmacokinetic variability and consequently a 12-h area under the curve (AUC(0-12)) should be used to guide the therapeutic dosage. However, patient compliance and economic costs make MPA AUC(0-12) an unpractical approach. Limited sampling strategies or predictive systemic drug exposure equation models based on limited sampling times are available only for MMF but lack for EC-MPS.
  
  
  METHODS
  The present study enrolled 26 kidney transplant recipients receiving EC-MPS as part of their immunosuppressive therapy. Twenty-six full MPA AUC(0-12) were performed. By using multiple stepwise regression analysis, we obtained several predictive equations of MPA systemic exposure in this group of patients. The value of the selected equations was tested in a subsequently enrolled group of 26 kidney transplant recipients.
  
  
  RESULTS
  The best equations obtained in the first group of patients were the following: 22.906 + 3.880·C(0) + 1.117·C(1) + 7.527·C(8) (r = 0.901) and 35.064 +3.784·C(0) + 1.002·C(1) + 1.192·C(2) (r = 0.846). These equation models showed an optimal agreement between the full AUCs and estimated AUCs by using the validation group of patients.
  
  
  CONCLUSIONS
  Limited sampling strategies are useful for MPA AUC(0-12) estimation in patients receiving EC-MPS and cyclosporine. The choice of one or the other equation model depends on the pharmacokinetic characteristics of the patients, in particular the potential presence of enterohepatic recirculation.
authors.affiliation: Department of Neurosciences, Unit of Clinical Pharmacology, School of Medicine, Federico II University, Naples, Italy. docapone@unina.it
authors.forename: Domenico
authors.initials: D
authors.lastname: Capone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tarantino
authors.forename: Irket
authors.initials: I
authors.lastname: Kadilli
authors.forename: Giuliano
authors.initials: G
authors.lastname: Polichetti
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Basile
authors.forename: Stefano
authors.initials: S
authors.lastname: Federico
authors.forename: Massimo
authors.initials: M
authors.lastname: Sabbatini
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000493:pharmacokinetics; D019540:Area Under Curve; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016903:Drug Monitoring; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007676:Kidney Failure, Chronic / Q000628:therapy*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics; D011379:Prognosis; D015996:Survival Rate; D013608:Tablets, Enteric-Coated / Q000008:administration & dosage* / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D011355:Prodrugs; D013608:Tablets, Enteric-Coated; D016572:Cyclosporine; D009173:Mycophenolic Acid