Table 1.
Summary of drug dependent parameters
| Tenofovir | Lamivudine | Emtricitabine | |
|---|---|---|---|
| PBPK model | Full | Full | Full |
| MW (g/mol) | 287 [34] | 229 [25] | 247 [10] |
| pKa | 3.7–6.5 [34] | 4.5 [25] | 2.65 [10] |
| logP | −2.21 [64] | −0.7 [9] | −0.43 [10] |
| fu | 0.993 [8] | 0.84a | 0.96 [10] |
| Main binding protein | Albumin | Albumin | Albumin |
| B/P ratio | 0.58 [65] | 1.3 [66] | 1 [10] |
| fa | 0.32 [18] | 0.89 [9] | 1 [10] |
| ka (h−1) | 1 [18] | 1.04 [24] | 0.54 [30] |
| Simcyp predicted Vss (L/kg) | 4.87b,c | 0.49b | 0.51b |
| Total CL (L/h) | 16.2 [17] | 23.9 [25] | 18 [31] |
| CLR (L/h) | 13.12 [17] | 16.8 [25] | 13 [10, 31] |
| CLad (L/h) | 3.1 [17] | 7.1 [25] | 5 [31] |
B/P ratio blood to plasma ratio, CL clearance, CLad additional systemic clearance, CLR renal clearance, fu free fraction, ka first order absorption rate, MW molecular weight, PBPK physiologically-based pharmacokinetic, pKa is the negative log of the acid dissociation constant, log P is the partition coefficient of the molecule between aqueous and lipophillic phases, fa is the fraction of the drug absorbed, Vss is the steady state volume of distribution
aSimcyp prediction toolbox
bPredicted using method 2
cPredicted using method 2, scaling factor of 17.88 optimised [20]