TABLE 5

Predicted and observed pharmacokinetic parameters of zidovudine and morphine in healthy subjects and those with Child Pugh C cirrhosis

PK ParametersHealthy SubjectsChild 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
Predicteda (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)
Observedb (mean ± S.D.)1.4 ± 0.438 ± 155.3 ± 1.610.2 ± 3.65.3 ± 1.610.2 ± 3.6
Predicted/observed ratio1.00.90.42.50.970.91
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)
Predicteda (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)
Observedc (mean ± S.D.)33.9c28 ± 2.380.411.4 ± 1.380.411.4 ± 1.3
Predicted/observed ratio1.2, 1.10.83, 0.980.811.30.971.08
  • 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.