TABLE 2.
Dose-dependent hepatotoxicity of RDV in healthy volunteers
| Cohort | n | Dosea (mg i.v.) | Total dose (mg) | Duration (days) | ALT/AST elevationsc |
|---|---|---|---|---|---|
| SAD 5 | 4 | 150 (solution) | 150 | 1 | 0/4 |
| SAD 8 | 4 | 150 (lyophilized powder) | 150 | 1 | 0/4 |
| SAD 6b | 4 | 225 (solution) | 225 | 1 | 0/4 |
| MAD 1 | 8 | 150 QD, 7 days | 1,050 | 7 | 2/8 |
| MAD 2 | 8 | 150 QD, 14 days | 2,100 | 14 | 6/8 |
a
Doses of RDV trialed in the SAD and MAD arms of the phase 1 trial for a 50- to 70-kg human (10). Long-term repeated dosing at 150 mg yields transaminase elevations.
b
No participants experienced transaminase elevations in the 225-mg SAD cohort.
c
Boldface indicates that transaminase elevations are dose dependent and emergent even in healthy human volunteers.