Physiologically Based Pharmacokinetic Modeling: Methodology, Applications, and Limitations with a Focus on Its Role in Pediatric Drug Development

Table 1

Physiological changes associated with liver cirrhosis (Child-Pugh score A–C) presented as fraction of control values from healthy individuals. The table is adapted from Edginton and Willmann [34].

Parameter	Child-Pugh class
	A	B	C
Blood flow
Portal	0.40	0.36	0.04
Hepatic arterial	1.3	2.3	3.4
Renal	0.88	0.65	0.48
Other organs	1.75	2.25	2.75
Cardiac index	1.11	1.27	1.36
Albumin	0.81	0.68	0.50
𝛼1-acid glycoprotein	0.60	0.56	0.30
Hematocrit value	0.39	0.37	0.35
Functional liver mass	0.69	0.55	0.28
Hepatic enzymes°
CYP3A4	1	0.4	0.4
CYP1A2	1	0.1	0.1
CYP2E1	1	0.83	0.83
GFR*	1	0.70	0.36

°Fractions of control enzyme activity; CYP = cytochrome P450; *GFR = glomerular filtration rate.