Table 1.
Physicochemical properties, in vitro and population pharmacokinetic data of anti-HIV drugs
| Rilpivirine (rat) | Rilpivirine (human) | Cabotegravir (human) | |
|---|---|---|---|
| log Po:w | 4.32 (53) | 4.32 (53) | 2.2 (23) |
| Protein binding | 99.7% (53) | 99.7% (53) | 99.3% (23) |
| pKa | 3.26 (53) | 3.26 (53) | 4.14 (23) |
| Blood-to-plasma ratio | 0.67 (53) | 0.67 (53) | 0.441 (23) |
| †4.5 (1A1) / 2.2 (1A9) | |||
| Plasma clearance | 1.3 L/kg/h | †2.04 (53) | (23) |
| IM release rate (h−1) | 2.6 × 10−2 | *9 × 10−4 | 4.54 × 10−4 (23) |
| Intradermal release rate (h−1) | ‡2 × 10−4 | - | - |
| Dose | 5, 20 mg/kg IM, 120 mg TD | - | - |
Values are presented as mean (reference). log Po:w – Partition coefficient between octanol and water; pKa – logarithmic value of the dissociation constant;
‡
Release rate followed a linear increase with respect to time shown in the following equation: (0.005/1344)*time+0.0002, time in hours.
†
Values represent intrinsic clearance in μl/min/pmol, rilpivirine is metabolised by CYP3A4, and cabotegravir by UGT1A1 and UGT1A9.
*
Release rate observed for an old formulation of rilpivirine derived using the PBPK model (38).