Deferasirox pharmacogenetic influence on pharmacokinetic, efficacy and toxicity in a cohort of pediatric patients.

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Allegra S, De Francia S, Cusato J, Arduino A, Massano D, Longo F, Piga A, D'Avolio A

Deferasirox pharmacogenetic influence on pharmacokinetic, efficacy and toxicity in a cohort of pediatric patients.

Pharmacogenomics. 2017 Apr;18(6):539-554. doi: 10.2217/pgs-2016-0176. Epub 2017 Mar 27.

PubMed ID

28346059 [ View in PubMed

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Abstract

AIM: We aimed to evaluate the influence of genetic polymorphisms involved in deferasirox metabolism and transport on its pharmacokinetics and treatment toxicity, in a cohort of beta-thalassaemic children. PATIENTS & METHODS: Drug plasma concentrations were measured by a HPLC-UV method. Allelic discrimination for UGT1A1, UGT1A3, CYP1A1, CYP1A2, CYP2D6, MRP2 and BCRP1 polymorphisms was performed by real-time PCR. RESULTS: CYP1A1 rs2606345AA influenced Ctrough (p = 0.001) and t1/2 (p = 0.042), CYP1A1 rs4646903TC/CC (p = 0.005) and BCRP1 rs2231142GA/AA (p = 0.005) influenced Tmax and CYP2D6 rs1135840CG/GG influenced Cmax (p = 0.044). UGT1A1 rs887829TT (p = 0.002) and CYP1A2 rs762551CC (p = 0.019) resulted as predictive factor of ferritin levels and CYP1A1 rs2606345CA/AA (p = 0.021) and CYP1A2 rs762551AC/CC (p = 0.027) of liver iron concentration. CONCLUSION: Our data suggest the usefulness of deferasirox pharmacogenetics in pediatric treatment optimization.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Deferasirox	UDP-glucuronosyltransferase 1-1	Protein	Humans	Unknown	Substrate Inhibitor	Details
Deferasirox	UDP-glucuronosyltransferase 1-3	Protein	Humans	Unknown	Inhibitor	Details