TABLE 1

Input parameters used for zidovudine physiologically based pharmacokinetic (PBPK) simulations

PBPK ParameterControlCirrhoticMethods/Reference
Molecular mass (g/mol)267.2Simcyp library
LogP0.05Simcyp library
Acid dissociation constant (pKa)9.7Simcyp library
Blood-to-plasma ratio0.91Simcyp library
Unbound fraction (Fu)0.8Simcyp library
Fraction absorbed (Fa)0.83Predicted by advanced dissolution, absorption, and metabolism model
ka (h−1)4.05Zhang and Unadkat (2017a)
Distribution modelMinimal PBPK model
Steady-state volume of distribution (Vss, liters/kg)1.1Zhang and Unadkat (2017a)
Renal clearance (liters/h)13.2Singlas et al. (1989), Taburet et al. (1990)
CLint,UGT2B7 (µl/min per milligram)29.56.5 (78% decrease)Estimated from literature (Singlas et al., 1989; Taburet et al., 1990) and based on protein abundance data
Additional clearance CLint, P450s, others (liters/h)3.071.01 (67% decrease)Estimated from literature (Stagg et al., 1992) and based on protein abundance data