title: Mycophenolate mofetil pharmacokinetic monitoring in pediatric kidney transplant recipients.
abstract: This open-label, longitudinal, long-term study of de novo pediatric renal transplant recipients was designed to investigate the pharmacokinetics (PK) of mycophenolic acid (MPA) and its possible interaction with cyclosporine (CsA). Thirty-four children on an immunosuppressive regimen of CsA, prednisone, and mycophenolate mofetil (MMF, 300-400 mg/m2 twice daily) were investigated at 6, 30, 180, and 360 days after transplantation. Considerable interindividual variability in the areas under the concentration curve (AUC(0-12)) of MPA was observed during the follow-up, although the dose of MMF remained the same over the same time. Predose levels (C0) increased significantly during the first 6 months after transplantation: C0 at 6 and 180 days after transplantation was 0.8 +/- 0.6 and 1.9 +/- 1.1 microg/mL (P < .0001). A significant time-dependent increase in the AUC of MPA was also observed during the first 6 posttransplant months: AUC(0-12) at 6 and 180 days after transplantation was 23.3 +/- 10.8 and 40 +/- 11.6 mg*h/L (P = .003). MPA concentrations 3 and 4 hours after MMF intake were the individual time points that best correlated with the full MPA AUC (r = 0.8 and 0.79; P < .001). The abbreviated MPA AUC (0-4 hours) correlated reasonably with the full AUC (r = 0.87; P < .001). Finally, a significant reduction in CsA dose during the first 6 posttransplant months (P < .001) matched the significant increases in both MPA C0 and full MPA AUC, thus demonstrating the interaction of the 2 immunosuppressive drugs. These observations suggest the need for therapeutic drug monitoring when adjusting the dose of MMF in children.
authors.affiliation: Pediatric Nephrology Unit, Pediatric Department, Ospedale Maggiore-Policlinico, IRCCS, Milan, Italy. lucianaghio@hotmail.com
authors.forename: L
authors.initials: L
authors.lastname: Ghio
authors.forename: M
authors.initials: M
authors.lastname: Ferraresso
authors.forename: S M
authors.initials: SM
authors.lastname: Viganò
authors.forename: F
authors.initials: F
authors.lastname: Ginevri
authors.forename: F
authors.initials: F
authors.lastname: Perfumo
authors.forename: B
authors.initials: B
authors.lastname: Gianoglio
authors.forename: L
authors.initials: L
authors.lastname: Murer
authors.forename: G
authors.initials: G
authors.lastname: Zacchello
authors.forename: L
authors.initials: L
authors.lastname: Dello Strologo
authors.forename: M
authors.initials: M
authors.lastname: Cardillo
authors.forename: S
authors.initials: S
authors.lastname: Tirelli
authors.forename: U
authors.initials: U
authors.lastname: Valente
authors.forename: A
authors.initials: A
authors.lastname: Edefonti
mesh_terms: D002648:Child; D016572:Cyclosporine / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology / Q000502:physiology*; D008657:Metabolic Clearance Rate; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011184:Postoperative Period
chemical_list: D016572:Cyclosporine; D009173:Mycophenolic Acid