Table 1.
Effects of a range of clinically used drugs on the E-M window and on the QTcB interval in anaesthetized guinea pigs
| Treatment | Baseline (actual units) | Dose 1 | Dose 2 | Dose 3 | Dose 4 | Dose 5 | |
|---|---|---|---|---|---|---|---|
| 10 min | 25 min | 40 min | 55 min | 70 min | |||
| Quinidine | E-M window | 28.4 ± 5.9 | −1.2 ± 1.7 | −7.7 ± 5.7 | −24.2 ± 8.8 | −43.6 ± 9.9** | −50.4 ± 8.9** |
| n = 4 | QTcB | 403.0 ± 6.2 | 7.9 ± 0.6 | 21.6 ± 4.3 | 46.5 ± 10.1* | 76.5 ± 11.4*** | 105.9 ± 14.2*** |
| Haloperidol | E-M window | 43.2 ± 4.0 | −3.6 ± 0.7 | −7.4 ± 2.2 | −21.3 ± 7.8 | −39.8 ± 7.7** | −66.0 ± 7.5*** |
| n = 3 | QTcB | 407.4 ± 6.8 | 13.7 ± 2.7 | 31.4 ± 7.2 | 47.2 ± 11.8* | 82.5 ± 6.6*** | 117.2 ± 15.8*** |
| Domperidone | E-M window | 37.3 ± 3.4 | −4.5 ± 1.7 | −10.5 ± 2.9 | −17.0 ± 3.8 | −34.0 ± 4.6*** | −48.0 ± 5.6*** |
| n = 4 | QTcB | 369.3 ± 10.0 | 11.8 ± 2.8 | 26.2 ± 3.9 | 37.5 ± 4.3*** | 68.9 ± 4.8*** | 88.3 ± 7.1*** |
| Terfenadine | E-M window | 32.8 ± 4.0 | −2.3 ± 2.1 | −7.9 ± 3.8 | −20.4 ± 5.3 | −28.0 ± 2.2 | −12.6 ± 17.9 |
| n = 4 | QTcB | 385.9 ± 5.2 | 10.6 ± 2.4 | 25.5 ± 2.1* | 54.5 ± 3.7*** | 79.8 ± 6.1*** | 92.5 ± 9.7*** |
| Thioridazine | E-M window | 28.2 ± 3.0 | −3.0 ± 1.3 | −7.4 ± 2.0 | −15.2 ± 3.9 | −20.9 ± 6.8* | −28.6 ± 6.8** |
| n = 5 | QTcB | 364.9 ± 11.6 | 11.5 ± 4.2 | 18.0 ± 2.9 | 27.6 ± 6.0* | 36.9 ± 7.8** | 53.1 ± 9.3*** |
| Vehicle | E-M window | 27.7 ± 9.2 | −1.7 ± 0.7 | −2.3 ± 0.9 | −3.2 ± 0.4 | −1.0 ± 2.6 | −2.3 ± 1.8 |
| n = 4 | QTcB | 365.3 ± 9.1 | 4.6 ± 2.2 | 7.5 ± 3.5 | −0.9 ± 7.2 | 0.7 ± 7.9 | 3.0 ± 7.9 |
| Diltiazem | E-M window | 40.2 ± 6.0 | 0.8 ± 4.9 | 3.4 ± 11.0 | 0.5 ± 16.4 | ||
| n = 4 | QTcB | 382.9 ± 17.2 | 7.1 ± 2.9 | 0.7 ± 8.9 | 5.6 ± 14.4 | ||
| Salbutamol | E-M window | 25.0 ± 5.3 | 4.4 ± 3.2 | 2.6 ± 2.7 | 2.2 ± 2.9 | 1.6 ± 3.4 | 0.1 ± 2.6 |
| n = 5 | QTcB | 372.1 ± 6.2 | −8.6 ± 4.4 | −15.7 ± 3.9 | −21.6 ± 6.9 | −27.3 ± 5.5** | −36.5 ± 5.8*** |
| Isoprenaline | E-M window | 25.0 ± 3.2 | 0.3 ± 1.4 | 1.6 ± 2.8 | 3.0 ± 5.1 | −19.5 ± 1.0** | −19.0 ± 4.1** |
| n = 4 | QTcB | 352.3 ± 3.8 | 6.6 ± 0.9 | 5.5 ± 4.4 | −41.4 ± 2.8*** | −38.1 ± 6.1*** | −44.2 ± 7.7*** |
| Amiodarone | E-M window | 26.3 ± 2.3 | −6.3 ± 1.9 | −10.5 ± 1.8 | −9.5 ± 2.2 | −6.0 ± 4.4 | 12 ± 2.4 |
| n = 4 | QTcB | 373.1 ± 2.3 | 13.6 ± 3.6 | 19.9 ± 3.2 | 26.1 ± 5.9* | 37.5 ± 7.7** | 38.2 ± 6.0** |
| Moxifloxacin | E-M window | 39.0 ± 5.0 | −2.0 ± 0.9 | −1.0 ± 2.8 | −3.0 ± 2.4 | −6.8 ± 2.8 | −13.5 ± 3.3* |
| n = 4 | QTcB | 364.6 ± 12.9 | 10.6 ± 1.1 | 18.8 ± 0.6 | 25.4 ± 1.7* | 33.6 ± 4.9** | 52.0 ± 6.4*** |
| Ciprofloxacin | E-M window | 37.5 ± 3.8 | −4.3 ± 1.3 | −4.5 ± 1.9 | −7.0 ± 2.0 | −9.8 ± 1.3 | −12.4 ± 4.0 |
| n = 4 | QTcB | 367.5 ± 13.7 | 4.0 ± 1.0 | 9.7 ± 9.6 | 8.5 ± 9.3 | 12.5 ± 10.5 | 22.0 ± 10.5 |
Baseline and changes from baseline (both in actual units, ms) for the E-M window and the QTcB interval after administration of a range of clinical reference drugs. Data show mean and SEM at the end of the drug infusion period. For isoprenaline (doses 4 and 5), the maximal effect (as shown in the table) was observed, respectively, 4 and 3 min after the start of the infusion. A one-way anova with Bonferroni post hoc test was performed on the ‘change from baseline’ values.
*
P < 0.05,
**
P < 0.01,
***
P < 0.001.