PK Parameters | Healthy Subjects | Child Pugh C Subjects (Original Simcyp Model) | Child Pugh C Subjects (Refined Simcyp Model Using Data Presented in this Article) | |||
---|---|---|---|---|---|---|

AUC (mg/liters per hour) | Oral CL (ml/min per kilogram) | AUC (mg/liters per hour) | Oral CL (ml/min per kilogram) | AUC (mg/lite per hour) | Oral CL (ml/min per kilogram) | |

Zidovudine | ||||||

Predicted^{a} (mean (5th–95th percentile range)) | 1.4 (0.5–2.6) | 35.2 (18.2–95.2) | 1.9 (0.7–3.8) | 25 (12.7–71.8) | 5.1 (2.2–9.2) | 9.3 (5.2–22) |

Observed^{b} (mean ± S.D.) | 1.4 ± 0.4 | 38 ± 15 | 5.3 ± 1.6 | 10.2 ± 3.6 | 5.3 ± 1.6 | 10.2 ± 3.6 |

Predicted/observed ratio | 1.0 | 0.9 | 0.4 | 2.5 | 0.97 | 0.91 |

Morphine | ||||||

AUC (µg/liters per hour) | i.v. CL (ml/min per kilogram) | AUC (µg/liters per hour) | IV CL (ml/min per kilogram) | AUC (µg/liters per hour) | IV CL (ml/min per kilogram) | |

Predicted^{a} (mean (5th–95th percentile range)) | 40.9 (30.2–54.8/) | 23.3 (17.4–31.5) | 65.3 (45.4–95.1) | 14.6 (10.0–21) | 77.7 (51.5–119.3) | 12.3 (8.0–18.5) |

Observed^{c} (mean ± S.D.) | 33.9^{c} | 28 ± 2.3 | 80.4 | 11.4 ± 1.3 | 80.4 | 11.4 ± 1.3 |

Predicted/observed ratio | 1.2, 1.1 | 0.83, 0.98 | 0.81 | 1.3 | 0.97 | 1.08 |

↵

^{a}Based on total of 100 simulations (10 virtual trials with 10 subjects). Mean, 5%–95% confidence intervals (CI) of the PK parameters were calculated by Non Compartment Analysis (NCA) (PK solver) of Simcyp-simulated plasma concentration-time profiles.↵

^{b}Observed PK parameters (Singlas et al., 1989; Taburet et al., 1990).↵

^{c}Observed PK parameters (Hasselstrom et al., 1990). Area under the curve (AUC) was calculated by NCA (PK solver) of digitized plasma concentration-time profiles.