New article "Forthcoming challenges in the management of STAT-C therapy" published online in Digestive and Liver Diseases(full article available in PDF format as well). This is the first article I've seen addressing the importance pharmacokinetics in STAT-C therapy and applies some of what we've learned from HIV antiretroviral therapy. Definitely worth a read - Cmin/IC50 ratios DO matter!!
Forthcoming challenges in the management of STAT-C therapy
Raffaele Bruno, Serena Cima, Laura Maiocchi, Paolo Sacchi
Received 22 July 2010; accepted 9 September 2010. published online 27 October 2010.
Corrected Proof
Abstract
Agents that specifically target the replication cycle of the virus [specifically targeted antiviral therapies for hepatitis C (STAT-Cs)] by directly inhibiting the NS3/4A serine protease, the NS5B polymerase and NS5A are currently in clinical development. The need to achieve serum drug concentrations able to suppress viral replication is a key factor for a successful antiviral therapy and the prevention of resistance. Thus pharmacokinetics parameters became important issues for drugs used in the therapy of hepatitis C. The ratio of Cmin/IC50 (inhibitory quotient or IQ) can provide a surrogate measure of a drug's ability to suppress HCV replication, by taking into account the relationship between plasma drug levels and viral susceptibility to the drug. Ritonavir boosting may be a useful strategy to improve pharmacokinetic parameters. Characterising resistance to STAT-Cs in clinical trials is essential for the management of a drug regimen to reduce the development of resistance and thereby maximise SVR rate. The lesson of HIV therapy, provide a compelling case for the exploration of combinations of direct-acting antiviral agents.
Subscribe to:
Post Comments (Atom)
Posts
No comments:
Post a Comment