Aim: We evaluated deferasirox pharmacokinetic according to SNPs in genes involved in its metabolism and elimination. Moreover, we defined a plasma area under the curve cut-off value predicting therapy response.
Patients & methods: Allelic discrimination was performed by real-time PCR. Drug plasma concentrations were measured by a high performance liquid chromatography system coupled with an ultraviolet method.
Results: Pharmacokinetic parameters were significantly influenced by UGT1A1 rs887829C>T, UGT1A3 rs1983023C>T and rs3806596A>G SNPs. Area under the curve cut-off values of 360 μg/ml/h for efficacy were here defined and 250 μg/ml/h for nonresponse was reported. UGT1A3 rs3806596GG and ABCG2 rs13120400CC genotypes were factors able to predict efficacy, whereas UGT1A3 rs3806596GG was a nonresponse predictor.
Conclusion: These data show how screening patient's genetic profile may help clinicians to optimize iron chelation therapy with deferasirox.
Keywords: ABCG2; SNPs; UGT1A1; UGT1A3; iron overload; pharmacokinetics.