Table 2.
Summary of CKA-Mediated Hepatotoxicity in Rat and Human SimPops and Preclinical and Clinical Observations
| Species | Rat | Rat | Human | Human | Human |
|---|---|---|---|---|---|
| Simulationsa | |||||
| Dose | 200 mg/kg | 500 mg/kg | 300 mg | 600 mg | 900 mg |
| Population size | n = 294 | n = 294 | n = 285 | n = 285 | n = 285 |
| ALT > 3× ULN (%)b | 2.4 | 36.4 | 0 | 0 | 0 |
| ALT > 5× ULN (%)b | 0 | 20.1 | 0 | 0 | 0 |
| ALT > 10× ULN (%)b | 0 | 7.8 | 0 | 0 | 0 |
| Preclinical/clinical trials | |||||
| Dose | 200 mg/kg | 500 mg/kg | 300 mg | 600 mg | 900 mg |
| Population size | n = 8 | n = 4 | n = 5 | n = 4 | n = 6 |
| ALT > 3× ULN (%)b | 25 | 75 | 0 | 0 | 16.7 |
| ALT > 5× ULN (%)b | 0 | 50 | 0 | 0 | 0 |
| ALT > 10× ULN (%)b | 0 | 25 | 0 | 0 | 0 |
a
Human simulations were run for 96 h, rat simulations for 72 h.
b
Upper limit of normal (ULN) was 30 U/L in rat simulations and preclinical trials. ULN was 40 U/L in human simulations and clinical trials.