5 Conclusion Almorexant has no influence on the pharmacokinetics and pharmacodynamics of warfarin. No dose adjustment of warfarin is necessary when concomitantly administered with almorexant. Acknowledgments This study was fully funded by Actelion Pharmaceuticals Ltd. Both authors are full-time employees of Actelion Pharmaceuticals Ltd. BAY 80-6946 supplier Jasper Dingemanse and Petra Hoever designed the study and revised the manuscript. Petra Hoever analyzed the data. The clinical part of the study was conducted at the
Privatklinik Leech, Graz, Austria with Fritz Pinl as principal investigator. The stereo-selective bioanalysis of warfarin was performed by Andreas Möller, Bioproof, München, Germany. Almorexant plasma concentrations were determined by Jürgen Karg,
Inovalab, Reinach, Switzerland. Editorial assistance for the preparation of the manuscript was provided by Paul van Giersbergen GF120918 chemical structure (Van Giersbergen Consulting, Wuenheim, France). Open AccessThis article is distributed under the terms of the Creative Commons Attribution Noncommercial find more License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. References 1. de Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci USA. 1998;95:322–7.PubMedCrossRef 2. Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998;92:573–85.PubMedCrossRef 3. Cao M, Guilleminault C. Hypocretin and its emerging role as a target for treatment of sleep disorders. Curr Neurol Neurosci Rep. 2011;11:227–34.PubMedCrossRef 4. Nattie E, Li A. Central chemoreception in wakefulness and sleep: evidence for a distributed network and a role for orexin.
J Appl Physiol. 2010;108:1417–24.PubMedCrossRef 5. Tsujino N, Sakurai T. Orexin/hypocretin: a neuropeptide at the interface of sleep, energy homeostasis, tetracosactide and reward system. Pharmacol Rev. 2009;61:162–76.PubMedCrossRef 6. Scammell TE, Winrow CJ. Orexin receptors: pharmacology and therapeutic opportunities. Annu Rev Pharmacol Toxicol. 2011;51:243–66.PubMedCrossRef 7. Coleman PJ, Renger JJ. Orexin receptor antagonists: a review of promising compounds patented since 2006. Expert Opin Ther Pat. 2010;20:307–24.PubMedCrossRef 8. Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S, et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med. 2007;13:150–5.PubMedCrossRef 9.
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