Fig 1.
Propofol concentration time profiles for each fetal-maternal sheep unit (n = 8).
Propofol was administered to the ewes as a bolus of 3 mg/kg, followed by an infusion of 450 μg/kg/min for 60 minutes. After that, propofol infusion rate was decreased to 75 μg/kg/min for 90 more minutes, and then stopped.
Fig 2.
The mean difference between maternal and fetal propofol plasma concentration in sheep after a bolus of propofol 3 mg/kg via the maternal femoral venous line, followed by an intravenous infusion of propofol (450 mcg/kg/min) for 60 minutes and then propofol infusion (75 mcg/kg/min) for 90 more minutes.
Table 1.
Plasma propofol concentration (μg/ml) in the ewes and the fetuses.
Fig 3.
The maternal- fetal pharmacokinetic model of propofol was best fitted using a 2 maternal compartment with a separate fetal compartment model. Vc = maternal central volume of distribution (L), Vp = maternal peripheral volume of distribution (L), Q = inter-compartmental clearance (L/min), CL = clearance from the maternal central compartment (L/min), QM-F = transfer rate between maternal and fetal compartment (L/min), VFetus = volume of distribution of fetal compartment (L).
Fig 4.
Between-subject random effects (η) for maternal clearance versus heart rate (HR) from the base (A) and final models (B).
Each box represents data from one sheep. The lines in the box correspond to median values; the bottom and top of the box are the first and third quartiles (the 25th and 75th percentiles); the upper whiskers extend from the box to the highest value within 1.5 times of inter-quartile range (IQR); the lower whisker extend from the box to the lowest value within 1.5 times of IQR. The individual variability (Random effect, η) for maternal clearance (ηCL) is narrower in the final model than in the base model.
Table 2.
Population pharmacokinetic parameter estimates of propofol in mid gestational maternal-fetal sheep.
Fig 5.
Goodness-of-fit plots for the final PK model.
(A) Population prediction versus observed concentration. (B) Individual prediction versus observed concentration. (C) Conditional weighted residuals (CWRES) versus population prediction. (D) Conditional weighted residuals (CWRES) versus time. Dashed red line, a locally weighted least-squares regression; solid black line, line of identity.
Fig 6.
Visual predictive check of prediction-corrected concentration of propofol in ewe and fetus for the final model.
Circles demonstrate prediction corrected observations. Red lines demonstrate 5th, 50th and 95th prediction percentiles.