| Autor: |
Almeida-Paulo GN; Department of Clinical Pharmacology, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain., Dapía García I; Instituto de Genética Médica y Molecular (INGEMM), La Paz University Hospital, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain., Lubomirov R; Department of Clinical Pharmacology, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain., Borobia AM; Department of Clinical Pharmacology, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain., Alonso-Sánchez NL; Department of Clinical Pharmacology, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain., Espinosa L; Department of Pediatric Nephrology, La Paz University Hospital, IdiPAZ, Madrid, Spain., Carcas-Sansuán AJ; Department of Clinical Pharmacology, La Paz University Hospital, School of Medicine, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain. |
| Abstrakt: |
Tacrolimus (TAC) is highly effective for the prevention of acute organ rejection. However, its clinical use may be challenging due to its large interindividual pharmacokinetic variability, which can be partially explained by genetic variations in TAC-metabolizing enzymes and transporters. The aim of this study was to evaluate the influence of genetic and clinical factors on TAC pharmacokinetic variability in 21 stable pediatric renal transplant patients. This study was nested in a previous Prograf to Advagraf conversion clinical trial. CYP3A5, ABCB1 and two POR genotypes were assessed by real-time PCR. The impact on TAC pharmacokinetics of individual genetic variants on CYP3A5 nonexpressors was evaluated by genetic score. Explicative models for TAC AUC 0-24h, C max and C min after Advagraf were developed by linear regression. The built genetic scores explain 13.7 and 26.5% of the total AUC 0-24h and C min total variability, respectively. Patients genetic information should be considered to monitorizate and predict TAC exposure. |
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