Tolerability, pharmacokinetics, and pharmacodynamics of single-dose almorexant, an orexin receptor antagonist, in healthy elderly subjects

Journal of Clinical Psychopharmacology

Volumn 33, Issue 3, 2013, Pages 363-370

  Hoever, Petra ^a   Hay, Justin ^b   Rad, Mandana ^b   Cavallaro, Marzia ^a   Van Gerven, Joop M ^b   Dingemanse, Jasper ^a  

^a ACTELION PHARMACEUTICALS LTD   (Switzerland)

^b CENTRE FOR HUMAN DRUG RESEARCH   (Netherlands)

Author keywords

almorexant; crexin receptor antagonist; elderly subjects; pharmacodynamics; pharmacokinetics

Indexed keywords

ALMOREXANT; PLACEBO; ZOLPIDEM;

ADULT; AGED; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; BODY EQUILIBRIUM; CLINICAL ARTICLE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG HALF LIFE; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; EUPHORIA; FATIGUE; FEMALE; HUMAN; INCIDENCE; MALE; MOOD; MUSCLE WEAKNESS; NAUSEA; NORMAL HUMAN; PERCEPTION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SACCADIC EYE MOVEMENT; SINGLE DRUG DOSE; SLEEP TIME; SOMNOLENCE;

ACETAMIDES; AGED; AGED, 80 AND OVER; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG ADMINISTRATION SCHEDULE; FEMALE; HALF-LIFE; HUMANS; ISOQUINOLINES; MALE; MIDDLE AGED; PYRIDINES; RECEPTORS, G-PROTEIN-COUPLED; RECEPTORS, NEUROPEPTIDE; SLEEP INITIATION AND MAINTENANCE DISORDERS;

EID: 84877584218     PISSN: 02710749     EISSN: 1533712X     Source Type: Journal    
DOI: 10.1097/JCP.0b013e31828f5a7a     Document Type: Article

References (41)

1. Colrain IM. Sleep and the brain. Neuropsychol Rev. 2011; 21: 1-4.
2. Neikrug AB, Ancoli-Israel S. Sleep disorders in the older adultVa mini-review. Gerontology. 2010; 56: 181-189.
3. Vitiello MV, Moe KE, Prinz PN. Sleep complaints cosegregate with illness in older adults: clinical research informed by and informing epidemiological studies of sleep. J Psychosom Res. 2002; 53: 555-559.
4. Foley DJ, Monjan AA, Brown SL, et al. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995; 18: 425-432.
5. Fetveit A. Late-life insomnia: a review. Geriatr Gerontol Int. 2009; 9: 220-234.
6. Wafford KA, Ebert B. Emerging anti-insomnia drugs: tackling sleeplessness and the quality of wake time. Nat Rev Drug Discov. 2008; 7: 530-540.
7. Nishino S. The hypocretin/orexin receptor: therapeutic prospective in sleep disorders. Expert Opin Investig Drugs. 2007; 16: 1785-1797.
8. de Lecea L, Kilduff TS, Peyron C, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998; 95: 322-327.
9. Sakurai T, Amemiya A, Ishii M, et al. Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell. 1998; 92: 573-585.
10. Chemelli RM, Willie JT, Sinton CM, et al. Narcolepsy in orexin knockout mice: molecular genetics of sleep regulation. Cell. 1999; 98: 437-451.
11. Lin L, Faraco J, Li R, et al. The sleep disorder canine narcolepsy is caused by a mutation in the hypocretin (orexin) receptor 2 gene. Cell. 1999; 98: 365-376.
12. Mieda M, Willie JT, Hara J, et al. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc Natl Acad Sci U S A. 2004; 101: 4649-4654.
13. Baumann CR, Bassetti CL. Hypocretins (orexins) and sleep-wake disorders. Lancet Neurol. 2005; 4: 673-682.
14. Peyron C, Faraco J, Rogers W, et al. A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nat Med. 2000; 6: 991-997.
15. Salomon RM, Ripley B, Kennedy JS, et al. Diurnal variation of cerebrospinal fluid hypocretin-1 (Orexin-A) levels in control and depressed subjects. Biol Psychiatry. 2003; 54: 96-104.
16. Igarashi N, Tatsumi K, Nakamura A, et al. Plasma orexin-A levels in obstructive sleep apnea-hypopnea syndrome. Chest. 2003; 124: 1381-1385.
17. Akanmu MA, Honda K. Selective stimulation of orexin receptor type 2 promotes wakefulness in freely behaving rats. Brain Res. 2005; 1048: 138-145.
18. Brisbare-Roch C, Dingemanse J, Koberstein R, et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nat Med. 2007; 13: 150-155.
19. Cruz H, Hoever P, Fiala-Buskies S, et al. Effect of ketoconazole on the pharmacokinetics and metabolism of almorexant, a dual orexin receptor antagonist. AAPS Annual Meeting. 2011: T3385.
20. Hoever P, de Haas S,Winkler J, et al. Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant. Clin Pharmacol Ther. 2010; 87: 593-600.
21. Hoever P, Dorffner G, Benes H, et al. Orexin receptor antagonism, a new sleep-enabling paradigm: a proof of concept clinical trial. Clin Pharmacol Ther. 2012; 91: 975-985.
22. Mangoni AA, Jackson SHD. Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications. Br J Clin Pharmacol. 2004; 57: 6-14.
23. Gandhi M, Aweeka F, Greenblatt RM, et al. Sex differences in pharmacokinetics and pharmacodynamics. Annu Rev Pharmacol Toxicol. 2004; 44: 499-523.
24. Borland RG, Nicholson AN. Human performance after barbiturate (heptabarbitone). Br J Clin Pharmacol. 1974; 1: 209-215.
25. Van Steveninck AL, Schoemaker HC, Pieters MS, et al. A study comparing the sensitivities of adaptive tracking, eye movement analysis and visual analogue lines to the effects of incremental doses of temazepam in healthy volunteers. Clin Pharmacol Ther. 1991; 50: 172-180.
26. de Haas SL, Franson KL, Schmitt JA, et al. The pharmacokinetic and pharmacodynamic effects of SL65.1498, a GABA-A >2,3 selective agonist, in comparison with lorazepam in healthy volunteers. J Psychopharmacol. 2009; 23: 625-632.
27. Bond A, Lader M. The use of analogue scales in rating subjective feelings. Br J Med Psychol. 1974; 47: 211-218.
28. Bowdle TA, Radant AD, Cowley DS, et al. Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations. Anesthesiology. 1998; 88: 82-88.
29. Anderer P, Gruber G, Parapatics S, et al. An E-health solution for automatic sleep classification according to Rechtschaffen and Kales: validation study of the Somnolyzer 24 - 7 utilizing the Siesta database. Neuropsychobiology. 2005; 51: 115-133.
30. Penzel T, Hirshkowitz M, Harsh J, et al. Digital analysis and technical specifications. J Clin Sleep Med. 2007; 3: 109-120.
31. Svetnik V, Ma J, Soper KA, et al. Evaluation of automated and semi-automated scoring of polysomnographic recordings from a clinical trial using zolpidem in the treatment of insomnia. Sleep. 2007; 30: 1562-1574.
32. Gough K, Hutchison M, Keene O, et al. Assessment of dose proportionality: report from the statisticians in the pharmaceutical industry/pharmacokinetics UK joint working party. Drug Inf J. 1995; 29: 1039-1048.
33. Actelion/GlaxoSmithKline. Actelion and GSK discontinue clinical development of almorexant. Available at: http: //www.actelion.com/en/investors/ media-releases/index.page?newsId=1483135. Accessed January 28, 2011.
34. Nishino S. The hypocretin/orexin receptor: therapeutic prospective in sleep disorders. Expert Opin Investig Drugs. 2007; 16: 1785-1797.
35. Cotreau MM, von Moltke LL, Greenblatt DJ. The influence of age and sex on the clearance of cytochrome P450 3A substrates. Clin Pharmacokinet. 2005; 44: 33-60.
36. Scharf MB, Mayleben DW, Kaffeman M, et al. Dose response effects of zolpidem in normal geriatric subjects. J Clin Psychiatry. 1991; 52: 77-83.
37. Salva P, Costa J. Clinical pharmacokinetics and pharmacodynamics of zolpidem. Therapeutic implications. Clin Pharmacokinet. 1995; 29: 142-153.
38. van Steveninck AL, van Berckel BN, Schoemaker RC, et al. The sensitivity of pharmacodynamic tests for the central nervous system effects of drugs on the effects of sleep deprivation. J Psychopharmacol. 1999; 13: 10-17.
39. Cysneiros RM, Farkas D, Harmatz JS, et al. Pharmacokinetic and pharmacodynamic interactions between zolpidem and caffeine. Clin Pharmacol Ther. 2007; 821: 54-62.
40. Roehrs T, Merlotti L, Zorick F, et al. Sedative, memory, and performance effects of hypnotics. Psychopharmacology. 1994; 116: 130-134.
41. Dingemanse J, Bury M, Bock J, et al. Comparative pharmacodynamics of Ro 41-3696, a new hypnotic, and zolpidem after night-time administration to healthy subjects. Psychopharmacology. 1995; 122: 169-174.