[Biochemical and pharmacological features of telaprevir]

Telaprevir is the first of a new generation of drugs based on blocking the NS3-4A protease of hepatitis C virus (HCV), which is essential for viral reproduction, and is especially active against genotype 1 HCV. However, to be effective, telaprevir must be combined with pegylated interferon and ribavirin for 12 weeks. Telaprevir has poor solubility in water and tends to crystallize, properties that hamper its formulation as a drug intended for oral delivery. This agent is efficiently absorbed after oral administration, but only if administered with food (not low in fat), since fasting intake markedly reduces systemic exposure. The total daily dose is 2,250 mg. Because of its pharmacokinetics, telaprevir has been designed for administration every 8 hours but efficacy is maintained in a twice-daily dosing regimen. Dose adjustment is not required in compensated liver cirrhosis. Because it is a substrate and potent inhibitor of CYP3A4 and glycoprotein P, telaprevir has multiple drug-drug interactions. The IL-28B genotype has little influence on the likelihood of response to telaprevir triple combination therapy.