2.1 PBPK model description
A full-body adult PBPK model was developed in SimBiology® a product of
MATLAB® software, version R2019a (MathWorks, Natick, USA; 2019).
Initially, a virtual cohort with 100 healthy individuals was simulated
for the validation of the nonpregnant adult PBPK model. The ratio of
male:female in this virtual cohort was 50:50 to represent the mixed
gender in the clinical studies within the nonpregnant population. For
the validation of the pregnancy PBPK model (developed from the adult
PBPK model; see section 2.7), another virtual cohort with 100 healthy
individuals (100% female) was simulated with the pregnancy PBPK model
to represent a pregnant population. For each model prediction, 4
different virtual cohorts were simulated, each with 100 healthy
individuals.
The distribution of other demographic characteristics (e.g. age, weight
and body mass index) of the virtual cohort was modelled to replicate the
individuals, where reported, in the clinical studies used for the model
qualification. Organ weights were determined using anthropometric
equations previously reported by Bosgra et al 2012 [27]. Organ
volumes were calculated from the organ weights and the respective organ
densities reported in literature [28]. Regional blood flow to organs
and tissue were calculated as fractions of the cardiac output [29].