Fig 1.
IVM plasma concentration vs. time after 200 μg/kg dosing (n = 56).
Table 1.
Subjects demographics and clinical characteristics.
Fig 2.
Schematic description of the selected population structural model.
Tlag, lag time function; TK0, zero dose input into absorption compartment; Ka, first–order absorption rate constant; VC/F, central volume of distribution; Vp/F, peripheral volume of distribution; CL/F, clearance; Q/F, intercompartmental clearance.
Fig 3.
The goodness of fit plots of final model Observed plasma concentrations of IVM versus individual predicted concentration (A) and population predicted concentration (B), conditional weighted residuals (CWRES) versus time after dose (C) and population predicted concentration (D).). Black lines in (A) and (B) are the line of identity. The blue line in (C) and (D) represent the locally weighted scatterplot smoothing line (LOWESS); dashed black lines are margins (y = 2) of outliers.
Table 2.
Final model estimations of population PK parameters of IVM.
Fig 4.
ETA box plots for sex impact on Vp/F.
Box plots show the impact of sex on Eta values of Vp/F in the base model (A) and after incorporating the sex effect in the final model (B). (0 = Female, 1 = male).
Fig 5.
Visual predictive check (VPC) of the final model over the time from 0 and 168 hr (Left) and over the time from 0 and 72 hr for external validation (right), following IVM oral administration (n = 1000).
A solid red line represents the 50th percentile of observed data (blue dots). Dashed red lines represent the 5th and 95th percentiles of observed data. Shaded areas (blue and red) represent a 95% prediction interval of the 5th, 50th, and 95th simulated data.
Fig 6.
Comparison of model–based simulated IVM exposure (Cmax, AUClast) across simulated dosing groups (18 mg, 200 μg/kg, and 36 mg) (upper panels) and simulated exposure stratified by sex (lower panels).
The box plot shows the median, 25th, and 75th quartiles.