Metabolism of Ramelteon in Human Liver Microsomes and Correlation with the Effect of Fluvoxamine on Ramelteon Pharmacokinetics

  title={Metabolism of Ramelteon in Human Liver Microsomes and Correlation with the Effect of Fluvoxamine on Ramelteon Pharmacokinetics},
  author={R. Scott Obach and Tim F. Ryder},
  journal={Drug Metabolism and Disposition},
  pages={1381 - 1391}
Ramelteon is a melatonin receptor agonist used as a treatment for insomnia. It is subject to a remarkably large drug-drug interaction (DDI) caused by fluvoxamine coadministration, resulting in a more than 100-fold increase in exposure. The objective of this study was to determine whether the DDI could be estimated using in vitro metabolism data. Ramelteon was shown to undergo hydroxylation in human liver microsomes to eight metabolites via six pathways. The main routes of metabolism included… 

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