Читать книгу Transporters and Drug-Metabolizing Enzymes in Drug Toxicity - Albert P. Li - Страница 65

The association of flucloxacillin‐induced liver toxicity with the HLA‐B*5701 genotype [95–97] represents the most successful application of GWAS in the identification of an at‐risk population based on genotype. Unfortunately, the association cannot be extended to other DILI drugs. Based on the metabolism of flucloxacillin to the cytotoxic metabolite 5‐hydroxymethyl flucloxacillin, patient populations with enhanced CYP3A4, CYP3A7, and CYP2C9 activities due to environmental and genetic factors, may be at risk of its hepatotoxicity. The findings with MRP2‐mediation of the localization of flucloxacillin in biliary cells suggest that increased MRP2 activity may also be a risk factor.