Table 3.
Overview Summary of the Effects of the 28 CIPA Drugs on the CTD90 Prolongation and Incidence of Early Afterdepolarizations (EADs), Measured From the Ca2+ Transient Imaging on hSC-CMs, at the 3 Test Sites
| Concentration (µM) |
CTD90 |
EAD Incidence |
|||||||
|---|---|---|---|---|---|---|---|---|---|
| Compound | Free Cmax | Tested Range | Ncardia | Janssen | MSD | Ncardia | Janssen | MSD | |
| High | Azimilide | 0.07 | 0.01–10 | Prolong | Prolong | Prolong | + | + | + |
| Bepridil | 0.032 | 0.01–10 | Prolong | Prolong | A | − | − | − | |
| d,l-Sotalol | 15 | 0.1–100 | Prolong | Prolong | Prolong | − | + | + | |
| Disopyramide | 0.7 | 0.1–100 | Prolong | Prolong | Prolong | − | + | + | |
| Dofetilide | 0.002 | 0.0003–0.01 | Prolong | Prolong | Prolong | + | + | + | |
| Ibutilide | 0.1 | 0.0001–0.1 | Prolong | Prolong | Prolong | + | + | + | |
| Quinidine | 3 | 1–30 | Prolong | Prolong | Prolong | + | + | + | |
| Vandetanib | 0.3 | 0.01–10 | Prolong | Prolong | Prolong | − | + | − | |
| Intermediate | Astemizole | 0.0003 | 0.0001–0.1 | Prolong | NE | Prolong | − | − | + |
| Chlorpromazine | 0.0345 | 0.1–3 | Prolong | Prolong | Prolong | − | − | − | |
| Cisapride | 0.00258 | 0.003–0.1 | Prolong | Prolong | Prolong | − | − | + | |
| Clarithromycin | 1.21 | 0.1–100 | Prolong | Prolong | NE | − | + | − | |
| Clozapine | 0.071 | 0.1–3 | Prolong | Short | Prolong | − | − | − | |
| Domperidone | 0.02 | 0.003–3 | Prolong | Prolong | Prolong | − | + | + | |
| Droperidol | 0.016 | 0.03–1 | Prolong | Prolong | Prolong | − | + | − | |
| Ondansetron | 0.37 | 0.03–30 | Prolong | Prolong | Prolong | − | + | + | |
| Pimozide | 0.00043 | 0.001–0.03 | NE | NE | Prolong | − | − | − | |
| Risperidone | 0.0018 | 0.003–0.1 | Prolong | Prolong | NE | − | − | − | |
| Terfenadine | 0.00029 | 0.001–1 | Prolong | Prolong | Prolong | − | − | − | |
| Low | Diltiazem | 0.13 | 0.01–10 | Short | Short | A | − | − | − |
| Loratadine | 0.00045 | 0.001–0.03 | NE | NE | NE | − | − | − | |
| Metoprolol | 1.8 | 3–100 | Prolong | Prolong | Short | − | − | − | |
| Mexiletine | 2.5 | 0.1–100 | Prolong | Prolong | Prolong | − | − | − | |
| Nifedipine | 0.0077 | 0.001–1 | Short | NE | NE | − | − | − | |
| Nitrendipine | 0.0030 | 0.01–0.3 | Short | Short | Short | − | − | − | |
| Ranolazine | 1.95 | 0.1–100 | Prolong | Prolong | A | − | − | − | |
| Tamoxifen | 0.021 | 0.1–3 | Prolong | NE | Short | − | − | − | |
| Verapamil | 0.045 | 0.001–1 | Short | Short | Short | − | − | − | |
NE, no effect (within vehicle tolerance interval range); A, no value because of the cell with beating stop or EAD at the dose; +, EAD presence. Prolong or short is determined by comparing for each concentration the ΔΔ% (net effect) versus the corresponding centered vehicle TI interval and then aggregate across the 4 tested concentrations per compound and per test site.