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].