Our PK/VD model provides a useful platform for the characterization of pharmacokinetic/pharmacodynamic relationships and the prediction of long-term virological response rates to aid future development of direct acting antiviral drugs. Both the rates were in general agreement. Finally, the PK/VD model was evaluated externally by comparing the expected and observed virological response rates during and post-treatment with DCV and ASV combination therapy in HCV GT1B patients. An empirical exponential function revealed that IC 50 changing over time described drug resistance in HCV GT1A patients during DCV or ASV monotherapy. A sigmoid E max function was applied to describe the antiviral effects of DCV and ASV, depending on the drug concentrations in the effect compartment. The IC 50 values of DCV and ASV were estimated to be 0.041 and 2.45 μg/L, respectively, in GT1A patients. On the basis of a constructed meta-database, an integrated PK/VD model was developed, which adequately described both DCV and ASV PK profiles and viral load time curves. In order to develop an integrated pharmacokinetic/viral dynamic (PK/VD) model to predict long-term virological response rates to daclatasvir (DCV) and asunaprevir (ASV) combination therapy in patients infected with genotype 1 (GT1) chronic hepatitis C virus (HCV), a systematic publication search was conducted for DCV and ASV administered alone and/or in combination in healthy subjects or patients with GT1 HCV infection.
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