[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.
Unidad de Gestión Clínica de Aparato Digestivo, Hospital Universitario Virgen de la Victoria, Facultad de Medicina, Universidad de Málaga, Málaga, España. Electronic address: andrade@uma.es.
Raúl J
RJ
Andrade
Javier
J
García-Samaniego
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000284:Administration, Oral; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D065692:Cytochrome P-450 CYP3A Inhibitors; D004359:Drug Therapy, Combination; D018565:Food-Drug Interactions; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D008658:Inactivation, Metabolic; D007372:Interferons / Q000008:administration & dosage / Q000627:therapeutic use; D007378:Interleukins / Q000235:genetics; D007408:Intestinal Absorption; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors*; D014779:Virus Replication / Q000187:drug effects; D000095022:Interferon Lambda; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000998:Antiviral Agents; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D007372:Interferons; D007378:Interleukins; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011480:Protease Inhibitors; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases; C093542:NS4 protein, hepatitis C virus; C486464:telaprevir; C510163:CYP3A4 protein, human
CYP3A4 inhibition; Farmacocinética de telaprevir; Inhibición CYP3A4; Inhibición NS3-4A; Metabolismo de telaprevir; NS3-4A inhibition; Telaprevir metabolism; Telaprevir pharmacokinetics