Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia.
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Karim A, Tolbert D, Cao C
Disposition kinetics and tolerance of escalating single doses of ramelteon, a high-affinity MT1 and MT2 melatonin receptor agonist indicated for treatment of insomnia.
J Clin Pharmacol. 2006 Feb;46(2):140-8.
- PubMed ID
- 16432265 [ View in PubMed]
- Abstract
Ramelteon is a selective MT(1)/MT(2) receptor agonist, indicated for insomnia treatment. Safety, tolerance, pharmacokinetics, and cognitive performance were evaluated following increasing ramelteon doses. Healthy adults (35-65 years) were randomly assigned to receive 1 of 5 oral ramelteon doses (4, 8, 16, 32, or 64 mg; n = 8 per group) or placebo (n = 20). C(max) and AUC(infinity) (mean [%CV]) increased with each dose: C(max) = 1.15 (109), 5.73 (97), 6.92 (77), 17.4 (76), and 25.9 (77) ng/mL, respectively, and AUC(infinity) = 1.71 (114), 6.95 (108), 9.88 (78), 22.5 (80), and 36.1 (71 n x h/mL), respectively. Mean T(max) values of 0.75 to 0.94 hours and mean elimination half-life of 0.83 to 1.90 hours remained relatively constant. Ramelteon was extensively metabolized. Besides ramelteon, 4 metabolites, M-I, M-II, M-III, and M-IV, were measured in serum. Metabolite M-II, which has shown weak ramelteon-like activity in vitro, was the major metabolite in serum. Digit Symbol Substitution Test and visual analog scale alertness scores were similar across all dose groups and did not differ from placebo. All adverse events were mild or moderate and resolved before study completion.
DrugBank Data that Cites this Article
- Drugs
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Ramelteon Melatonin receptor type 1A Protein Humans YesMultitargetDetails Ramelteon Melatonin receptor type 1B Protein Humans YesMultitargetDetails