Age and gender effects on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic agent acting via melatonin receptors MT1 and MT2.

Article Details

Citation

Copy to clipboard

Greenblatt DJ, Harmatz JS, Karim A

Age and gender effects on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic agent acting via melatonin receptors MT1 and MT2.

J Clin Pharmacol. 2007 Apr;47(4):485-96.

PubMed ID

17389558 [ View in PubMed

]

Abstract

Effects of age and gender on the pharmacokinetics and pharmacodynamics of ramelteon, a hypnotic acting via binding to melatonin MT(1) and MT(2) receptors, were evaluated in healthy young (18-34 years) and elderly (63-79 years) volunteers. Part 1 evaluated the pharmacokinetics of open-label oral ramelteon, 16 mg. Part 2 was a double-blind, randomized, 2-trial crossover pharmacodynamic study of 16-mg ramelteon and matching placebo. Ramelteon clearance was significantly reduced in elderly vs young volunteers (384 vs 883 mL/min/kg, P<.01) and half-life significantly increased (1.9 vs 1.3 h, P<.001). Gender did not significantly influence clearance or half-life. Ramelteon was extensively transformed to its hydroxylated M-II metabolite, with serum AUC values averaging about 30 times those of the parent drug. Compared to placebo, ramelteon increased self- and observer-rated sedation, but age and gender did not influence the magnitude of the ramelteon-placebo difference. Ramelteon did not significantly impair digit-symbol substitution test performance or impair information acquisition and recall. Thus, the reduced clearance and higher serum levels of ramelteon in elderly subjects were not associated with enhanced pharmacodynamic effects. The usually recommended clinical dose of ramelteon (8 mg) does not require modification based on age or gender.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Ramelteon	Melatonin receptor type 1A	Protein	Humans	Yes	Multitarget	Details
Ramelteon	Melatonin receptor type 1B	Protein	Humans	Yes	Multitarget	Details