Drug parameters relevant for clinical extrapolation of in vitro transport inhibition

DrugMol. Wt.DoseCmaxfuCmax,uIgutReference
Dolutegravir441.36508.32a0.010.08a453.14Tivicay, Prescribing Information, 2018
Cabotegravir427.333014.880.010.15280.81Ford et al., 2019
Bictegravir449.385013.690.010.14445.06Biktarvy, Prescribing Information, 2018
Raltegravir482.514004.500.170.763315.99Isentress (raltegravir) Prescribing Information, 2019
Elvitegravir447.88852.68b0.020.05b759.13Viteka Prescribing Information, 2015
Elvitegravir447.881503.35b0.020.07b1339.64Viteka Prescribing Information, 2015
Methotrexate454.44100.570.50.2888.02Jylamvo (methotrexate) Prescribing Information, 2017
Methotrexate (i.v.)454.44153.800.51.90N/ASeideman et al., 1993
Pemetrexed (i.v.)597.49500 mg/m2189.120.1935.93N/AKavathiya et al., 2017
  • Cmax,u, unbound Cmax (i.e., Cmax * fu); fu, plasma fraction unbound; Igut, theoretical gut concentration (oral dose/250 ml) or highest soluble aqueous concentration; oral administration in all cases, unless noted); N/A, not applicable (i.v. administration).

  • a Most commonly used 50-mg daily regimen; 50 mg twice daily; Cmax = 9.4 μM and Cmax,u = 0.09 μM (ViiV Healthcare, 2018), twice-daily dosing does not impact extrapolation values or results in Fig. 6.

  • b Not cobicistat boosted, 150-mg dose cobicistat-boosted Cmax = 3.8 μM and Cmax,u = 0.08 μM (2019); cobicistat boosting does not impact extrapolation values or results in Fig. 6.