title: Limited sampling strategy for prolonged-release tacrolimus in renal transplant patients by use of the dried blood spot technique.
abstract: OBJECTIVE
  The aim of this study was to develop a clinically applicable limited sampling strategy for ambulatory Caucasian kidney transplant patients to estimate area under the curve in a 24-h period (AUC0-24) of prolonged-release tacrolimus.
  
  
  METHODS
  Twenty six kidney recipients, at least 6 months after transplantation, receiving prolonged-release tacrolimus, were enrolled. In each patient, seven blood samples were collected during a period of 24 h by use of the validated dried blood spot method. Best subset selection multiple linear regression was performed to derive limited sampling strategy (LSS). The equations were constrained to include a maximum of three samples collected within 4 h after the intake to maintain clinical applicability. To assess the predictive performance of LSS, residuals for each patient were calculated based on models fitted to a dataset where that patient was omitted.
  
  
  RESULTS
  The prediction formula for the AUC(0-24) using the time points 0, 2, and 4 h after ingestion (C(0h)-C(2h)-C(4h)) provided the highest correlation with the AUC(0-24) (r(2) = 0.95): AUC0-24 = 44.9 + 8.9 × C(0h) + 2.1 × C(2h) + 7.6 × C(4h). Measures for bias and precision, i.e., median percentage prediction error (MPPE) and median absolute prediction error (MAPE), were 0.4 and 4.8%, respectively. For the same patients, the correlation between C(24h) and AUC0-24 was worse (r(2) = 0.77) while MPPE and MAPE were 6.2 and 7.2%, respectively.
  
  
  CONCLUSIONS
  In the outpatient department, a LSS using C(0h)-C(2h)-C(4h) can be used for reliable estimation of the AUC(0-24) of prolonged-release tacrolimus.
authors.affiliation: Department of Nephrology, Radboud university medical center, PO box 9101, 6500 HB, Nijmegen, The Netherlands, gerben.vanboekel@radboudumc.nl.
authors.forename: G A J
authors.initials: GA
authors.lastname: van Boekel
authors.forename: A R T
authors.initials: AR
authors.lastname: Donders
authors.forename: K E J
authors.initials: KE
authors.lastname: Hoogtanders
authors.forename: T R A
authors.initials: TR
authors.lastname: Havenith
authors.forename: L B
authors.initials: LB
authors.lastname: Hilbrands
authors.forename: R E
authors.initials: RE
authors.lastname: Aarnoutse
mesh_terms: D000328:Adult; D019540:Area Under Curve; D065095:Calcineurin Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D059788:Dried Blood Spot Testing; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016030:Kidney Transplantation / Q000009:adverse effects; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D011446:Prospective Studies; D016559:Tacrolimus / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D065095:Calcineurin Inhibitors; D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus