title: Universal approach to pharmacokinetic monitoring of immunosuppressive agents in children.
abstract: Current data indicate that pharmacokinetic (PK) monitoring of cyclosporin microemulsion (CsA) should be performed using the 2-h concentration (C2), that tacrolimus (Tac) is commonly monitored using the trough level, and mycophenolate mofetil (MMF) should be monitored using the 1-h (C1), 2-h (C2) and 6-h (C6) concentrations. The three differing time-point requirements are cumbersome, and we aimed to develop universal guidelines for all three drugs using a large number of full PK profiles in children. One-hundred and twenty two stable pediatric patients, receiving either CsA (165 PK profiles, 69 patients, 24 with concomitant MMF) or Tac (122 PK profiles, 53 patients, 18 with MMF) were analyzed retrospectively. Pearson r for the CsA C2 was 0.90 [95% confidence interval(CI): 0.86-0.92], for Tac C2 r was 0.86 (95% CI: 0.80-0.90), and for MPA C2 r was 0.77 (95% CI: 0.68-0.83), respectively. For MPA, at least three time-points are required to accurately estimate the area under the concentration-time curve (AUC), and C1, C2 and C6 serve as best markers. Excellent AUC estimations could be obtained from a limited sampling strategy from C1, C2 and C6 or C0, C1, C2 and C4 with clinically acceptable errors for all three drugs. The AUC can be estimated with great precision by using an identical approach for all three drugs. Target AUCs for a given time-point after transplantation remain to be established.
authors.affiliation: Division of Pediatric Nephrology, Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, 401 Smyth Road, Ottawa, Ontario, Canada K1H 8L1. filler@cheo.on.ca
authors.forename: G
authors.initials: G
authors.lastname: Filler
authors.forename: J
authors.initials: J
authors.lastname: Feber
authors.forename: N
authors.initials: N
authors.lastname: Lepage
authors.forename: G
authors.initials: G
authors.lastname: Weiler
authors.forename: I
authors.initials: I
authors.lastname: Mai
mesh_terms: D000293:Adolescent; D019540:Area Under Curve; D002648:Child; D016572:Cyclosporine / Q000493:pharmacokinetics*; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016030:Kidney Transplantation / Q000502:physiology; D008991:Monitoring, Physiologic; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D016559:Tacrolimus / Q000493:pharmacokinetics*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus