Читать книгу Transporters and Drug-Metabolizing Enzymes in Drug Toxicity - Albert P. Li - Страница 89

The major risk factor associated with terfenadine cardiotoxicity is its coadministration with drugs that are potent inhibitors of CYP3A4 such as ketoconazole, fluconazole, itraconazole, erythromycin, clarithromycin, cimetidine, and troleandomycin [200–204]. Patients with low CYP3A4 activities due to genetic polymorphism or liver diseases may also be at high risk due to lower hepatic clearance of terfenadine [189]. There is evidence that grapefruit juice, a known inhibitor of intestinal CYP3A4 and the enteric efflux transporter Ppg, would increase plasma terfenadine concentration to detectable levels with QT prolongation effects [205–208]. The clinical significance of the grapefruit juice effects is yet to be substantiated.