Table 1.
Physicochemical Properties and In Vitro and Population Pharmacokinetic Data of Cabotegravir, Rilpivirine, and Rifampicin
| Property | Cabotegravir | Rilpivirine | Rifampicin |
|---|---|---|---|
| Molecular weight | 427 | 366 | 823 |
| Log Po:w | 1.04 [18] | 4.32 [19] | 2.7 [20] |
| Protein binding | 99.3% [21] | 99.7% [19] | 80.0% [22] |
| pKa | 10.04 [18] | 3.26 [19] | 1.7 [20] |
| R | .441 [23] | .67 [19] | .9 [24] |
| Polar surface area | 99.2 | 97.42 | 220.15 |
| Hydrogen bond donors | 2 | 2 | 6 |
| Caco-2 permeability, cm/sec | Not available | 12 × 10-6 [19] | 5.79 × 10-6 [25] |
| Apparent clearance, L/h | NA | NA | 10.3 (7.49–12.0) [26] |
| CYP3A4, CLint | NA | 2.04 [19] | NA |
| UGT1A1, CLint | 4.5 [27] | NA | NA |
| UGT1A9, CLint | 2.2 [27] | NA | NA |
| Release rate, h-1 | 4.5 × 10-4 [28] | 9 × 10-4 [8] | NA |
| Indmax/Ind50 CYP3A4 | NA | NA | 15/ .715 [29] |
| UGT clearance | NA | NA | ↑2.4 fold [10] |
Abbreviations: CLint, intrinsic clearance; CYP, cytochrome P450 (µL/minute/pmol); Ind50, 50% maximal induction; Indmax, maximum induction potential; log Po:w, partition coefficient between octanol and water; NA, not applicable; pKa, logarithmic value of the dissociation constant; R, blood-to-plasma drug ratio; UGT, uridine diphosphate glucuronosyltransferase (µL/minute/mg);.