Parameter | Symbol (unit of measure) | Population mean estimate (SE [%]) | CV^{c} of estimate for between-curve variability (SE [%]) |
---|---|---|---|

PD parameters | |||

Log_{10} of 2nd-order infection rate constant | k_{infect} | −4.10 (2.39) | 0.0841 (128^{b}) |

Synthesis rate constant of virus | k_{syn} (1/h) | 9.35 (7.09) | 0.068 (219) |

Mean delay time until release of virus in the absence of drug | T_{Delay} = 5/k_{tr} (h) | 40.0 (2.56) | 0.0238 (97) |

Mean survival time of infected cells | MST_{Infected} = 1/k_{death} (h) | 70.5 (8.92) | 0.152 (141) |

Mean survival time for extracellular virus | MST_{Virus} = 1/k_{loss,virus} (h) | 14.3 (10.4) | 0.172 (112) |

Log_{10} initial no. of uninfected cells | Log_U | 6.30 (fixed) | 0 (fixed) |

Log_{10} initial no. of infected cells | Log_I | 3.38 (2.66) | 0.365 (29) |

Maximum extent of inhibition by FAV | I_{maxFAV} (normal scale) | 0.9999 (∼0.9992–1.00^{a}) | 0.793^{a} (88.8) |

FAV concn causing 50% I_{max} | IC_{50_FAV} (μM) | 41.7 (2.55) | 0.039 (180) |

Hill coefficient of FAV | Hill_{FAV} | 2.79 (4.53) | 0.1 (fixed) |

Maximum extent of inhibition by RBV | I_{maxRBV} (normal scale) | 0.954 (∼0.924–0.973^{a}) | 0.44^{a} (120) |

RBV concn causing 50% I_{max} | IC_{50_RBV} (μg/ml) | 7.86 (9.99) | 0.491 (84.3) |

Hill coefficient of RBV | Hill_{RBV} | 2.90 (16.5) | 0.1 (fixed) |

Maximum extent of inhibition by IFN | I_{maxIFN} (normal scale) | 0.99997 (∼0.99990–1.00^{a}) | 0.859^{a} (62.4) |

IFN concn causing 50% I_{max} | IC_{50_IFN} (IU/ml) | 4.12 (15.9) | 0.131 (383) |

Hill coefficient of IFN | Hill_{IFN} | 2.00 (fixed) | 0.1 (fixed) |

Interaction factor between FAV and RBV | PSI = 1 if monotherapy, PSI = SYNANT^{d} if combination therapy | 1.37 (8.21) | 0.05 (427) |

Maximum extent of cytotoxicity by RBV | MST_{TOX} = 1/S_{maxRBV} (h) | 11.9 (7.21) | 0.354 (39.3) |

RBV concn causing 50% S_{max} | SC_{50_RBV} (μg/ml) | 150 (11.3) | 0.226 (110) |

Hill coefficient of RBV for toxicity | Hill_{RBVTOX} (normal scale) | 4.16 (12.5) | 0.1 (fixed) |

Residual-error parameter | |||

Additive error for viral load on log_{10} scale | SDin | 0.333 (4.67) |

↵a

*I*_{max}was assumed to be normally distributed on a logistically transformed scale (*I*_{maxTransformed}). The population mean value of*I*_{max}is reported on a normal scale (i.e., from 0 to 1), whereas the between-curve variability is presented as the standard deviation of a normal distribution on a logistically transformed scale.↵b Between-curve variability was included and required in this population PD model to account for minor biological differences between experimental curves on separate days. The uncertainty (percent standard error) for the estimated between-curve variability tended to be large for some parameters. However, this has only a minor or no effect on the predictive performance of the model, as shown by the NPDE.

↵c CV, coefficient of variation.

↵d SYNANT, synergy or antagonism.