Parameter^{a} | Base model | Final model | ||
---|---|---|---|---|

Estimate | Error (CV%) | Estimate | Error (CV%) | |

Population mean | ||||

CL (liter/h) | 0.369 | 2.2 | 0.356 | 2.5 |

V1 (liter) | 1.21 | 14.4 | 1.21 | 10.7 |

Q (liter/h) | 5.54 | 13.9 | 5.54 | 12.7 |

V2 (liter) | 4.62 | 3.4 | 4.62 | 3.2 |

Allometric scaling exponent | 0.790 | 4.0 | 0.787 | 3.7 |

Fixed-effect exponent of AST | NA^{c} | NA | −0.0601 | 36.6 |

Fixed-effect exponent of total bilirubin | NA | NA | −0.0492 | 47.0 |

Intersubject variability | ||||

ω_{CL}^{2} | 0.0835 | 13.1 | 0.0763 | 12.0 |

ω_{V}_{1}^{2} | 0.967 | 18.4 | 0.953 | 18.6 |

ω_{Q}^{2} | 1.52 | 13.9 | 1.52 | 13.1 |

ω_{V}_{2}^{2} | 0.0276 | 39.9 | 0.0277 | 40.1 |

Residual error | ||||

ε_{prop}^{2} | 0.0313 | 8.2 | 0.0313 | 8.2 |

ε_{prop-2}^{2}^{b} | 0.129 | 21.7 | 0.130 | 21.8 |

ε_{const}^{2} | 0.00443 | 56.7 | 0.00461 | 54.9 |

↵a AST, aspartate aminotransferase; CL, clearance from the central compartment; CV%, coefficient of variation; PK, pharmacokinetic;

*Q*, intercompartmental clearance;*V*1, volume of the central compartment;*V*2, volume of the peripheral compartment; ε_{prop}, proportional residual error; ε_{const}, constant residual error; ω, variance of the intersubject variability of the specified parameter.↵b Different proportional error applied to patients (

*n*= 25) in study 9463-CL-2101 with highly variable trough screen data.↵c NA, not applicable.