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.

From: On the potential of in vitro organ-chip models to define temporal pharmacokinetic-pharmacodynamic relationships

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 Chen56; Pratt et al.55