Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia

Journal of Clinical Pharmacology

Volumn 46, Issue 2, 2006, Pages 140-148

  Karim, Aziz ^a   Tolbert, Dwain ^a   Cao, Charlie ^a  

^a TAKEDA PHARMACEUTICALS   (United States)

Author keywords

High affinity melatonin MT1 MT2 receptor; Insomnia; Pharmacokinetics; Single rising doses; Tolerance

Indexed keywords

HYPNOTIC AGENT; MELATONIN 1 RECEPTOR; MELATONIN 2 RECEPTOR; MELATONIN RECEPTOR AGONIST; PLACEBO; RAMELTEON; THYROTROPIN; UNCLASSIFIED DRUG;

ADULT; ALERTNESS; AREA UNDER THE CURVE; ARTICLE; CLINICAL TRIAL; COGNITION; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DOSE TIME EFFECT RELATION; DRUG ABSORPTION; DRUG DISPOSITION; DRUG METABOLISM; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG SELECTIVITY; DRUG STRUCTURE; FEMALE; HUMAN; INSOMNIA; MALE; NAUSEA; NORMAL HUMAN; RANDOMIZED CONTROLLED TRIAL; SCORING SYSTEM; SINGLE DRUG DOSE; SOMNOLENCE; THYROID DISEASE; THYROTROPIN BLOOD LEVEL; VISUAL ANALOG SCALE;

ADULT; AGED; AREA UNDER CURVE; ATTENTION; BIOTRANSFORMATION; COGNITION; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; INDENES; MALE; MIDDLE AGED; NEUROPSYCHOLOGICAL TESTS; PSYCHOMOTOR PERFORMANCE; RECEPTORS, MELATONIN; SLEEP INITIATION AND MAINTENANCE DISORDERS;

EID: 31344480674     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270005283461     Document Type: Article

References (15)

1. Ramelteon [package insert]. Lincolnshire, Ill: Takeda Pharmaceuticals North America; 2005.
2. Kato K, Hirai K, Nishiyama K, et al. Neurochemical properties of ramelteon (TAK-375), a selective MT1/MT2 receptor agonist. Neuropharmacology. 2005;48:301-310.
3. Stubbs CM, Karim A. A safety, tolerance, and pharmacokinetic study of five single doses of TAK-375 in healthy adults [abstract]. Sleep. 2003;26(suppl):A76.
4. Hibberd M, Stevenson SJ. A phase-I open-label study of the absorption, metabolism, and excretion of (14C)-ramelteon (TAK-375) following a single oral dose in healthy male subjects [abstract]. Sleep. 2004;27(suppl);A54.
5. Amakye DD, Hibberd M, Stevenson SJ. A phase I study to investigate the absolute bioavailability of a single oral dose of ramelteon (TAK-375) in healthy male subjects [abstract]. Sleep. 2004;27(suppl):A54.
6. Karim A, Tolbert D, Cao C, Zhao Z. Effect of food on the systemic exposure of ramelteon (TAK-375) following a single dose. J Clin Pharmacol. 2004;44:1210.
7. Metropolitan Life Insurance Company. 1983 Metropolitan height and weight tables. Stat Bull Metropol Life Found. 1983;64:3-9.
8. Cough 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.
9. Roth T, Stubbs C, Walsh J. Ramelteon (TAK-375), a selective MT1/ MT2 receptor agonist, reduces latency to persistent sleep in a model of transient insomnia related to a novel sleep environment. Sleep. 2005;28:303-307.
10. Roth T, Seiden D, Zee P, et al. Phase III outpatient trial of ramelteon for the treatment of chronic insomnia in the elderly [abstract]. J Am Geriatr Soc. 2005;53(suppl 4):S25.
11. Zammit G, Roth T, Erman M, Sainati S, Weigand S, Zhang J. Double-blind, placebo-controlled polysomnography and outpatient trial to evaluate the efficacy and safety of ramelteon in adult patients with chronic insomnia [abstract]. Sleep. 2005;28(suppl):A228.
12. Prescott E, Clayton R, Pethen S, Hibberd M, Turcan R. Identification of metabolites in human urine following administration of (14C)-ramelteon (TAK-375). Drug Metab Rev. 2004;36(suppl 1):203.
13. Greenblatt DJ, Harmatz JS, Karim A. Effect of age and gender on the pharmacokinetics of ramelteon (TAK-375), a novel selective ML-1 receptor agonist [abstract]. J Am Geriatr Soc. 2004;52(suppl 1):S125.
14. Erman M, Seiden D, Zammit G, Sainati S, Zhang J. An efficacy, safety, and dose-response study of Ramelteon in patients with chronic primary insomnia. Sleep Med. In press.
15. Griffiths R, Suess P, Johnson M. Ramelteon and triazolam in humans: behavioral effects and abuse potential [abstract]. Sleep. 2005;28(suppl):A44.