Limited Sampling Strategies for Monitoring Tacrolimus in Pediatric Liver Transplant Recipients
- 1 August 2011
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Therapeutic Drug Monitoring
- Vol. 33 (4), 380-386
- https://doi.org/10.1097/ftd.0b013e318220bc64
Abstract
Objective: To develop and validate limited sampling strategies (LSSs) for tacrolimus in pediatric liver transplant recipients. Methods: Thirty-six 12-hour pharmacokinetic profiles from 28 pediatric liver transplant recipients (0.4-18.5 years) were collected. Tacrolimus concentrations were measured by immunoassay and area under the curve (AUC0-12) was determined by trapezoidal rule. LSSs consisting of 1, 2, 3, or 4 concentration-time points were developed using multiple regression analysis. Eight promising models (2 per category) were selected based on the following criteria: r2 ≥ 0.90, inclusion of trough concentration (C0), and time points within 4 hours postdose. The predictive performance of these LSSs was evaluated in an independent set of data by measuring the mean prediction error and the root mean squared prediction error. Results: Five models including 2-4 time points predicted AUC0-12 with a ±15% error limit. Bias (mean prediction error) and precision (root mean squared prediction error) of LSS involving C0, C1, and C4 (AUCpredicted = 9.30 + 3.69 × C0 + 2.19 × C1 + 4.69 × C4) were −4.98% and 8.29%, respectively. Among single time point LSSs, the model using C0 had a poor correlation with AUC0-12 (r2 = 0.53), whereas the one with C4 had the highest correlation with tacrolimus exposure (r2 = 0.84). Conclusions: Trough concentration is a poor predictor of tacrolimus AUC0-12 in pediatric liver transplant recipients. However, LSSs using 2-4 concentration-time points obtained within 4 hours postdose provide a reliable and convenient method to predict tacrolimus exposure in this population. The proposed LSSs represent an important step that will allow the undertaking of prospective trials aiming to better define tacrolimus target AUC in pediatric liver transplant recipients and to determine whether AUC-guided monitoring is superior to C0-based monitoring in terms of efficacy and safety.Keywords
This publication has 39 references indexed in Scilit:
- Pharmacokinetics of tacrolimus in stable paediatric renal transplant recipientsPediatric Nephrology, 2010
- Once-Daily Tacrolimus Extended-Release Formulation: 1-Year Post-Conversion in Stable Pediatric Liver Transplant RecipientsAmerican Journal of Transplantation, 2007
- Contributions of the Transplant Registry: The 2006 Annual Report of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS)*Pediatric Transplantation, 2007
- Improved pharmacokinetic monitoring of tacrolimus exposure after pediatric renal transplantationPediatric Transplantation, 2007
- The pharmacokinetics and immunosuppressive response of tacrolimus in paediatric renal transplant recipientsPediatric Nephrology, 2006
- Effect of age, ethnicity, and glucocorticoid use on tacrolimus pharmacokinetics in pediatric renal transplant patientsPediatric Transplantation, 2005
- Pharmacokinetics of Sirolimus and Tacrolimus in Pediatric Transplant PatientsAmerican Journal of Transplantation, 2004
- Universal approach to pharmacokinetic monitoring of immunosuppressive agents in childrenPediatric Transplantation, 2002
- Efficacy and pharmacokinetics of tacrolimus oral suspension in pediatric liver transplant recipientsPediatric Transplantation, 2002
- Pharmacokinetics of tacrolimus (FK 506) in children and adolescents with renal transplants.Nephrology Dialysis Transplantation, 1997