2.1 Model construction
The whole PBPK models for LPV/r, and chloroquine were constructed based
on the previously published articles (Saeheng, Na-Bangchang, Siccardi,
Rajoli, & Karbwang, 2019; Siccardi, 2015) using Simbiology® (version
5.8.2), the product of MATLAB® (version 2019a) (MathWorks, Natick, MA,
USA). The physicochemical, and biochemical properties (model parameters)
of each drug were collected from the published articles (Table S1)
(Ernest, Hall, & Jones, 2005; Koudriakova et al., 1998; Olafuyi &
Badhan, 2019; Patel, Mandava, Gokulgandhi, Pal, & Mitra, 2014; Saeheng
et al., 2019; Wagner et al., 2017; Xu, Vela, Shi, Marroum, & Gao, 2017;
Zhang et al., 2012). Model assumptions included blood-flow limited
model, immediate drug dissolution, absence of drug absorption in the
stomach and large intestine, and absence of enterohepatic recirculation.
The hepatic fraction of metabolism by cytochrome P450 (CYP) 3A4
(fm, CYP3A4), and the fraction of metabolism by CYP2D6
(fm, CYP2D6) were assumed to be 0.61, and 0.39,
respectively (Projean et al., 2003).