Table 1 Qualitative comparison of the effects of terfenadine in the MPS systems compared to conventional approaches applied during early drug discovery to detect changes in QT prolongation23,24,55,56,57.
Model | Assay/endpoints | Result | Dosing Scheme | Time Frame | Reference |
|---|---|---|---|---|---|
Heart only MPS | FPD | +4.4% at 1.912 μM | Nominal dose at time 0 | Average observed data over 24 hours | — |
Heart:Liver MPS | FPD | +1.9% at 0.228 μM | Nominal dose at time 0 | Average observed data over 24 hours | — |
CHO cells overexpressing hERG/Kv11.1 | hERG inhibition (electrophysiology) | IC50 0.02–0.2 μM | Non-cumulative concentration response curve | 3–5 minutes | Redfern et al.57 |
Anaesthetised Guinea pig | QTc | +8% at 0.0384 μM | IV infusion for 10 minutes | Peak measurements post infusion (10–40 minutes) | Yao et al.23 |
Anaesthetised Guinea pig | QTc | +2.8% at 0.0069 μM | IV infusion for 10 minutes | Peak measurements post infusion (10–40 minutes) | Yao et al.23 |
Dog Telemetry | QTc | +2.34% at 0.026 μM | IV infusion over 180 minutes | Average measurements from 150–180 minutes | Ollerstam et al.24 |
Dog Telemetry | QTc | +1.72% at 0.0078 μM | IV infusion over 180 minutes | Average measurements from 150–180 minutes | Ollerstam et al.24 |
Human | QTc | +1.5% at approx 0.004 μM | 2X daily 60 mg dose orally | QTc measured day 1–5 |
