Drug Development
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18 Lu, HR, Vlaminckx, E, Van de Water, A, Rohrbacher, J, Hermans, A, Gallacher, DJ. In- vitro experimental models for the risk assessment of antibiotic-induced QT prolongation. Eur J Pharmacol 2007; 577(1-3):222-232. 19 Antzelevitch, C, Belardinelli, L, Zygmunt, AC, Burashnikov, A, Di Diego, JM, Fish, JM et al. Electrophysiological effects of ranolazine, a novel antianginal agent with antiarrhythmic properties. Circulation 2004; 110(8):904-910. 20 Lacerda, AE, Kuryshev, YA, Chen, Y, Renganathan, M, Eng, H, Danthi, SJ et al. Alfuzosin delays cardiac repolarization by a novel mechanism. J Pharmacol Exp Ther 2008; 324(2):427-433. 21 Rodriguez-Menchaca, AA, Navarro-Polanco, RA, Ferrer- Villada, T, Rupp, J, Sachse, FB, Tristani-Firouzi, M et al. The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel. Proc Natl Acad Sci U S A 2008; 105(4): 1364-1368. 22 Gintant, G. An evaluation of hERG current assay performance: Translating preclinical safety studies to clinical QT prolongation. Pharmacol Ther 2011; 129(2):109-119.
prolongation is due to hERG channel blockade. A direct assay of hERG channel inhibition is there- fore routinely part of the safety pharmacology package conducted to support initiation of clinical trials. Several medium or high-throughput auto- mated patch clamp platforms have become avail- able that make it possible to move the hERG assay earlier in the preclinical phase to early lead optimi- sation. This strategy can help to improve the suc- cess rate of drug candidates. To support this new testing strategy, WIL Research now offers the CytoPatch automated patch clamp platform. Evaluation of this platform has shown that there is a high correlation with manual patch clamping. Of the automated patch clamp platforms tested, the CytoPatch platform most closely mimics manual patch clamping. Since the correlation between hERG inhibition and drug-induced long QT syndrome is not per- fect, the testing of drug effects on other ion chan- nels is recommended to be included in future in vitro testing strategies.
DDW
Beppy van de Waart is Head of the In Vitro & Environmental Toxicology Department at WIL Research, a global CRO whose focus is to custom design product safety toxicological research. Under her responsibility genetic toxicology, in vitro toxicology, in vitro ADME, in vitro safety pharmacology and ecotox studies (GLP and non- GLP) are designed, executed and reported and new studies are developed.
Dr Walter Westerink is Study Director at the In Vitro & Environmental Toxicology Department at WIL Research. He is involved in genotoxicity, in vitro safety pharmacology and in vitro toxicology studies and development of new studies. Before joining WIL Research in September 2011, he held various positions in the pharmaceutical industry where he was involved in mechanistic and inves- tigative toxicology and early ADME and toxicity screening.
Dr Nuria Piñeiro Costas has been Study Director at the In Vitro & Environmental Toxicology Department at WIL Research since 2006. She is involved in all in vitro ADME studies and in vitro safety pharmacology studies. Before joining WIL Research, she held different research positions in university and industry.
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