TABLE 2

Parameters used in predictions of the 3D regimen as perpetrators of enzyme and transporter inhibition using basic and mechanistic static models

DrugMolecular WeightDosefu,pfu,bCmax,ss or [I]1[I]h[I2]Fa or FaFgKa
g/molmgng/mlh−1
Paritaprevir765.891500.0200.029147054.660010.25
Ritonavir720.961000.0110.018160032.510010.17
Ombitasvir894.12250.00030.00031270.140010.21
Dasabuvir493.582500.0040.006103014.8100010.58
M1509.580.0660.094660
• Dashes indicate that parameters were not calculated for the metabolite, since it was not dosed orally. Generally, fu,p was determined from in vitro studies, where the tested concentration of each drug is near its Cmax,ss. Fu,b was calculated from fu,p and the blood-to-plasma ratio. [I]h is the hepatic inlet concentration as described in eq. 1. [I]2 is oral dose amount of inhibitor/250 ml as described in eq. 2. Fa and Fg are fractions of the dose of inhibitor that was absorbed and escaped gut metabolism/extraction, respectively. Ka was estimated from clinical population PK analysis (Mensing et al., 2016).