Clinical assessment of drug-drug interactions of tasimelteon, a novel dual melatonin receptor agonist.

Article Details

Citation

Ogilvie BW, Torres R, Dressman MA, Kramer WG, Baroldi P

Clinical assessment of drug-drug interactions of tasimelteon, a novel dual melatonin receptor agonist.

J Clin Pharmacol. 2015 Sep;55(9):1004-11. doi: 10.1002/jcph.507. Epub 2015 May 7.

PubMed ID
25851638 [ View in PubMed
]
Abstract

Tasimelteon ([1R-trans]-N-[(2-[2,3-dihydro-4-benzofuranyl] cyclopropyl) methyl] propanamide), a novel dual melatonin receptor agonist that demonstrates specificity and high affinity for melatonin receptor types 1 and 2 (MT1 and MT2 receptors), is the first treatment approved by the US Food and Drug Administration for Non-24-Hour Sleep-Wake Disorder. Tasimelteon is rapidly absorbed, with a mean absolute bioavailability of approximately 38%, and is extensively metabolized primarily by oxidation at multiple sites, mainly by cytochrome P450 (CYP) 1A2 and CYP3A4/5, as initially demonstrated by in vitro studies and confirmed by the results of clinical drug-drug interactions presented here. The effects of strong inhibitors and moderate or strong inducers of CYP1A2 and CYP3A4/5 on the pharmacokinetics of tasimelteon were evaluated in humans. Coadministration with fluvoxamine resulted in an approximately 6.5-fold increase in tasimelteon's area under the curve (AUC), whereas cigarette smoking decreased tasimelteon's exposure by approximately 40%. Coadministration with ketoconazole resulted in an approximately 54% increase in tasimelteon's AUC, whereas rifampin pretreatment resulted in a decrease in tasimelteon's exposure of approximately 89%.

DrugBank Data that Cites this Article

Drug Enzymes
DrugEnzymeKindOrganismPharmacological ActionActions
TasimelteonCytochrome P450 1A2ProteinHumans
Unknown
Substrate
Details
TasimelteonCytochrome P450 3A4ProteinHumans
No
Substrate
Details