Viral hepatitis C therapy: pharmacokinetic and pharmacodynamic considerations.
Chronic hepatitis C is a global health problem. To prevent or reduce complications, the hepatitis C virus (HCV) infection needs to be eradicated. There have been several developments in treating these patients since the discovery of the virus. As of 1 January 2014, the drugs that are approved for treatment of chronic HCV infection are peginterferon-α, ribavirin, boceprevir, telaprevir, simeprevir and sofosbuvir. In this review we provide an overview of the clinical pharmacokinetic characteristics of these agents by describing their absorption, distribution, metabolism and excretion. In the pharmacodynamic part we summarize what is known about the relationships between the pharmacokinetics of each drug and efficacy or toxicity. We briefly discuss the pharmacokinetics and pharmacodynamics of chronic hepatitis C treatment in special patient populations, such as patients with liver cirrhosis, renal insufficiency or HCV/HIV coinfection, and children. With this knowledge, physicians, pharmacists, nurse practitioners, etc. should be educated to safely and effectively treat HCV-infected patients.
Department of Pharmacy, 864 Radboud university medical center, Geert Grooteplein 10, 6525 GA, Nijmegen, The Netherlands, Klaartje.deKanter@radboudumc.nl.
Clara T M M
CT
de Kanter
Joost P H
JP
Drenth
Joop E
JE
Arends
Henk W
HW
Reesink
Marc
M
van der Valk
Robert J
RJ
de Knegt
David M
DM
Burger
D000998:Antiviral Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D004347:Drug Interactions; D019698:Hepatitis C, Chronic / Q000378:metabolism*; D006575:Heterocyclic Compounds, 3-Ring / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D016898:Interferon-alpha / Q000493:pharmacokinetics / Q000494:pharmacology; D008103:Liver Cirrhosis / Q000378:metabolism; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000494:pharmacology; D011392:Proline / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D012254:Ribavirin / Q000493:pharmacokinetics / Q000494:pharmacology; D000069616:Simeprevir; D000069474:Sofosbuvir; D013449:Sulfonamides / Q000493:pharmacokinetics / Q000494:pharmacology; D014542:Uridine Monophosphate / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology
D000998:Antiviral Agents; D006575:Heterocyclic Compounds, 3-Ring; D016898:Interferon-alpha; D009842:Oligopeptides; D013449:Sulfonamides; D012254:Ribavirin; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline; D000069616:Simeprevir; D014542:Uridine Monophosphate; D000069474:Sofosbuvir