Value of non-clinical cardiac repolarization assays in supporting the discovery and development of safer medicines

British Journal of Pharmacology

Volumn 159, Issue 1, 2010, Pages 25-33

  Valentin, Jean Pierre ^a   Pollard, Chris ^a   Lainée, Pierre ^a   Hammond, Tim ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

Hazard identification; QT interval prolongation; Risk assessment; Risk management and mitigation

Indexed keywords

BIOLOGICAL MARKER; CARDIAC AGENT; COMPOUND Z; ONDANSETRON; RANOLAZINE; RAXENA; SIBENADET; UNCLASSIFIED DRUG;

CLINICAL RESEARCH; COMBINATION CHEMOTHERAPY; COMPUTER MODEL; DRUG SAFETY; DRUG TARGETING; HEART ARRHYTHMIA; HEART REPOLARIZATION; HUMAN; MEDICAL DECISION MAKING; MONOTHERAPY; NONHUMAN; PRIORITY JOURNAL; REASSURANCE; REVIEW; RISK ASSESSMENT; RISK MANAGEMENT;

ANIMALS; CLINICAL TRIALS AS TOPIC; DRUG APPROVAL; DRUG DESIGN; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; HUMANS; LONG QT SYNDROME; PHARMACEUTICAL PREPARATIONS; RISK ASSESSMENT;

EID: 74549182596     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/j.1476-5381.2009.00530.x     Document Type: Review

References (26)

1. Abi-Gerges N, Valentin JP, Pollard CE (2010) Beagle dog left ventricular midmyocardial myocytes for in vitro assessment of drug-induced delayed repolarisation Action potential short-term variability may predict the proarrhythmic potential of a drug. Br J Pharmacol 159 : 77 92.
2. Anonymous (2000). ICHS7A: safety pharmacology studies for human pharmaceuticals. CPMP/ICH/539/00. London, November 16, 2000. [WWW document]. URL http://www.emea.europa.eu/pdfs/human/ich/042302en.pdf [accessed on 23 October 2009 2005a)
3. Anonymous (2000).ICH S7B: the nonclinical evaluation of the potential for delayed ventricular repolarization (QT interval prolongation) by human pharmaceuticals. London, 25 May 2005. CPMP/ICH/423/02. [WWW document]. URL http://www.emea.europa.eu/pdfs/human/ich/053900en.pdf [accessed on 23 October 2009 2005b)
4. Anonymous (2000). ICH E14: the clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. London, 25 May 2005. CPMP/ICH/2/04. [WWW document]. URL http://www.emea.europa.eu/pdfs/ human/ich/000204en.pdf [accessed on 23 October 2009
5. Armstrong D, Migeon J, Rolf MG, Bowes J, Crowford M, Valentin JP (2008). Secondary pharmacodynamic studies and in vitro pharmacological profiling. In : Gad SC (ed.). Preclinical Development Handbook: Toxicology. Wiley Publishers : Hoboken, NJ, pp. 581 610.
6. Benedict CR, Arbogast R, Martin L, Patton L, Morrill B, Hahne W (1996). Single-blind study of the effects of intravenous dolasetron mesylate versus ondansetron on electrocardiographic parameters in normal volunteers. J Cardiovasc Pharmacol 28 : 53 59.
7. Bridgland-Taylor MH, Hargreave AC, Orme E, A, Harmer A, Henthorn A, Ding DC et al. (2006). Optimisation and validation of a medium-throughput electrophysiology-based hERG assay using IonWorks™ HT. J Pharmacol Toxicol Methods 54 : 189 199.
8. De Bruin ML, Pettersson M, Meyboom RH, Hoes AW, Leufkens HG (2005). Anti-HERG activity and the risk of drug-induced arrhythmias and sudden death. Eur Heart J 26 : 590 597.
9. Gavaghan CL, Arnby CH, Blomberg N, Strandlund G, Boyer S (2007). Development, interpretation and temporal evaluation of a global QSAR of hERG electrophysiology screening data. J Comput Aided Mol Des 21 : 189 206.
10. Hinterseer M, Thomsen MB, Beckmann BM, Pfeufer A, Schimpf R, Wichmann HE et al. (2008). Beat-to-beat variability of QT intervals is increased in patients with drug-induced long-QT syndrome: a case control pilot study. Eur Heart J 29 : 185 190.
11. Hoffmann P, Warner B (2006). Are hERG channel inhibition and QT interval prolongation all there is in drug-induced torsadogenesis? A review of emerging trends. J Pharmacol Toxicol Methods 53 : 87 105.
12. Lawrence CL, Pollard CE, Hammond TG, Valentin JP (2008). In vitro models of proarrhythmia. Br J Pharmacol 154 : 1516 1522.
13. Lesson PD, Springthorpe B (2007). The influence of drug-like concepts on decision-making in medicinal chemistry. Nat Rev Drug Discov 6 : 881 890.
14. Newbold P, Sanders N, Reele SB (2007). Lack of correlation between exercise and sibenadet-induced changes in heart rate corrected measurement of the QT interval. Br J Clin Pharmacol 63 : 279 287.
15. Pugsley MK, Authier S, Curtis MJ (2008). Principles in safety pharmacology. Br J Pharmacol 154 : 1382 1399.
16. Redfern WS, Wakefield ID, Prior H, Hammond TG, Valentin JP (2002). Safety pharmacology - a progressive approach. Fundam Clin Pharmacol 16 : 161 173.
17. Redfern WS, Carlsson L, Davis AS, Lynch WG, MacKenzie I, Palethorpe S et al. (2003). Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. Cardiovasc Res 58 : 32 45.
18. Sanguinetti MC, Jiang C, Curran ME, Keating MT (1995). A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81 : 299 307.
19. Schroeder K, Neagle B, Trezise DJ, Worley J (2003). IonWorks HT: a new high-throughput electrophysiology measurement platform. J Biomol Screen 8 : 50 64.
20. Shah RR (2010). Drug-induced QT interval shortening: potential implications and regulatory perspectives. Br J Pharmacol 159 : 58 69.
21. Trepakova ES, Koerner J, Pettit SD, Valentin JP HESI Pro-Arrhythmia Committee (2009). A HESI consortium approach to assess the human predictive value of non-clinical repolarization assays. J Pharmacol Toxicol Methods 60 : 45 50.
22. Valentin JP, Hammond TG (2006). Safety pharmacology: past, present and future. In : Smith CG, O'Donnell J (eds). The Process of New Drug Discovery and Development. Informa Healthcare : New York, NY, USA, pp. 243 290.
23. Valentin JP, Hammond TG (2008). Safety and secondary pharmacology: successes, threats, challenges and opportunities. J Pharmacol Toxicol Methods 58 : 77 87.
24. Valentin JP, Newbold P, Hammond TG (2006). Predictive value of non-clinical models to assess QT liability in man: Sibenadet (viozan, AR-C68397AA), a case study. J Pharmacol Toxicol Methods 54 : 253.
25. Valentin JP, Abi-Gerges N, Hammond TG (2007). Ranolazine: non-clinical safety pharmacology studies supporting regulatory approval? In : Sietsema WK, Schwen R (eds). Nonclinical Drug Safety Assessment - Practical Considerations for Successful Registration. FDA News : Falls Church, VA, USA, pp. 539 555.
26. Wallis R (2010). Integrated risk assessment and predictive value to humans of non-clinical repolarization assays. Br J Pharmacol 159 : 115 121.