TABLE 4.
Cardiotoxicity of WX-081 and bedaquiline in beagle dogsa
| Cardiac indicators | ECG parameters | WX-081 | Bedaquiline fumarate |
|---|---|---|---|
| hERG IC50 (uM) | >30.00 | >30.00 | |
| IC50 of metabolite | 1.89 | 1.73 | |
| AUC0-24h metabolite-to-parent ratio | 0.039-0.44 | 0.082-0.60 | |
| cTnI (pg/mL) | 440 (1/3 male) | ||
| ECG | HR | Slowing of the heart rate | An increased incidence of first- and second-degree atrioventricular block |
| RR/PR interval | Lengthening of the RR interval | Prolongation of PR interval | |
| QT interval | Physiologically appropriate lengthening of the QT interval | Significant QT interval prolongation |
a
Fourteen days repeated oral dose toxicity and toxicokinetic, head-to-head study in beagle dogs. hERG IC50, half-maximum inhibitory concentration of the hERG channel; AUC0-24h, time curve in a dosing interval of 24 h; cTnI, cardiac troponin I; ECG, electrocardiogram; HR, heart rate.