Table 2.
Predicted Relative Channel Block and Changes in ECG Biomarkers at Cmax
| Dofetilide | Quinidine | Ranolazine | Verapamil | |
|---|---|---|---|---|
| Population's Cmax | 2.7±0.3 ng/mL | 1.8±0.4 μg/mL | 2.3±1.4 μg/mL | 130.4±75.8 ng/mL |
| Relative block | ||||
| hERG, % | ∼55 | ∼71 | ∼26 | ∼7 |
| Calcium, % | No block | ∼8 | No block | ∼17 |
| Late sodium, % | No block | ∼3 | ∼21 | No block |
| ECG intervals | ||||
| QTc, milliseconds | 73.6‡ (65.8 to 81.5) | 78.9‡ (68.2 to 89.7) | 12.0† (7.3 to 16.7) | — |
| JTpeakc, milliseconds | 39.1‡ (31.6 to 46.6) | 26.1† (13.5 to 38.7) | — | — |
| Tpeak‐Tend, milliseconds | 34.4‡ (26.9 to 42.0) | 51.2‡ (34.6 to 67.8) | 10.0‡ (7.3 to 12.7) | 3.6* (1.9 to 5.4) |
| T wave morphology | ||||
| Flatness, d.u. | 0.16‡ (0.14 to 0.18) | 0.21‡ (0.19 to 0.23) | 0.06‡ (0.05 to 0.08) | — |
| Asymmetry, d.u. | 0.25‡ (0.16 to 0.34) | 0.34† (0.20 to 0.48) | 0.10† (0.05 to 0.15) | — |
| Notch, % | 55.0‡ (25.2 to 81.6) | 69.7‡ (43.2 to 87.5) | 1.4† (0.2 to 9.4) | — |
| Repolarization duration | ||||
| ERD30%, milliseconds | 23.3‡ (16.0 to 30.6) | 22.1† (13.9 to 30.3) | 10.2‡ (7.3 to 13.2) | — |
| LRD30%, milliseconds | 13.0‡ (7.4 to 18.6) | 25.8‡ (15.4 to 36.3) | 3.5† (0.9 to 6.0) | — |
| Vectorcardiographic | ||||
| QRS‐T angle, ° | −3.9‡ (−5.4 to −2.4) | 2.7* (−0.3 to 5.8) | — | 0.4* (−1.0 to 1.9) |
| TCRT, radians | 0.08‡ (0.04 to 0.11) | — | — | −0.01* (−0.04 to 0.02) |
| Tmagmax, μV | −145.9‡ (−176.5 to −115.2) | −169.5‡ (−209.3 to −129.7) | −66.6† (−90.3 to −42.9) | — |
| Ventricular gradient, mV ms | — | — | — | — |
Drug concentrations mean ± SD. Relative ion channel block is from the Hill equation curve shown in Figure 2 at Cmax. ECG biomarker changes reported as mean values and 95% confident intervals. d.u. indicates dimensionless units; ECG, electrocardiogram; ERD30%, 30% of early repolarization duration; hERG, hERG potassium channel; LRD30%, 30% of late repolarization duration; QRS‐T, angle between the mean QRS and T vectors; QTc, Fridericia's heart rate corrected QT; TCRT, total cosine R‐to‐T; Tmagmax, maximum magnitude of the T vector.
*P<0.05; †P<0.01; ‡P<0.001; (—) means there was no relationship between drug concentration and the ECG biomarker.