P30 Limited sampling strategies to predict valganciclovir exposure in kidney transplanted children
| Autor: | A Facchin, N Benyoub, S Magreault, Evelyne Jacqz-Aigrain, Valery Elie |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Ganciclovir
medicine.medical_specialty education.field_of_study medicine.diagnostic_test business.industry Population Area under the curve Renal function Valganciclovir Transplantation Pharmacokinetics Therapeutic drug monitoring Internal medicine Pediatrics Perinatology and Child Health medicine education business medicine.drug |
| Zdroj: | Archives of Disease in Childhood. 104:e29.2-e29 |
| ISSN: | 1468-2044 0003-9888 |
| DOI: | 10.1136/archdischild-2019-esdppp.68 |
| Popis: | BackgroundGanciclovir and its pro-drug, valganciclovir, are anti-viral drugs used in cytomegalovirus infections treatment in kidney transplanted children. Both present a high pharmacokinetic variability requiring dosage individualization and Therapeutic Drug Monitoring to ensure optimal therapeutic exposure. This retrospective monocentric study aimed to develop a Limited Sampling Strategy (LSS) predicting Area Under the Curve (AUC0-24h) reducing the number of blood samples to improve and facilitate kidney transplanted children medical care.MethodsPediatric kidney transplanted children treated with valganciclovir were included. Rich pharmacokinetic data from ganciclovir plasmatic dosages (sampling times at 0h, 1h, 2h, 4h, 8h, 12 h and 24 h) were collected between February 2005 and November 2018. Ganciclovir exposures at steady-state (AUC0-24h) were calculated using the trapezoidal method. The LSS was developed using a multilinear regression approach to predict AUC0-24h. The overall patients population was divided into two groups for model development and validation purposes.Results129 patients were included: 46 girls and 83 boys, mean age at transplantation was 11.3years ± 5.1. Multilinear regression models were developed on 85 pharmacokinetic profiles (85 patients, mean AUC0-24h=64µg.h/mL ± 27, creatinine clearance=72.4 mL/min per 1.73 m2) and validated on an independent group of 73 pharmacokinetic profiles (44 patients). Regressions based on samples collected at 0, 2, 4 h (R=0.946) or 0, 2, 8 h (R=0.968) presented the best AUC0-24h predictive performances (RMSE=7.5 and 6.6, MAE=5.7 and 4.8 respectively) with an average difference between reference and predicted AUC0-24h of -0.52 and 0.67µg.h/mL respectively.ConclusionsTo date, this is the largest cohort of valganciclovir treated pediatric transplanted children used to develop a LSS. This LSS allows to accurately predict ganciclovir AUC0-24h in pediatric transplanted patients using 3 pharmacokinetic blood samples at 0h, 2h, and 4 h post-dose. Beside other Bayesian estimators developed in the literature, this multilinear regression can be easily implemented into daily practice facilitating patients care.Disclosure(s)Nothing to disclose |
| Databáze: | OpenAIRE |
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