Effect of alosetron on the pharmacokinetics of fluoxetine.

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D'Souza DL, Dimmitt DC, Robbins DK, Nezamis J, Simms L, Koch KM

Effect of alosetron on the pharmacokinetics of fluoxetine.

J Clin Pharmacol. 2001 Apr;41(4):455-8.

PubMed ID

11304903 [ View in PubMed

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Abstract

Lotronex (alosetron hydrochloride) is a 5-HT3 receptor antagonist indicated for the treatment of irritable bowel syndrome (IBS) in females whose predominant bowel habit is diarrhea. Alosetron is extensively metabolized by multiple cytochrome P450 (CYP) enzymes, including CYP2C9 and CYP3A4. Fluoxetine is an antidepressant that is administered as a racemic mixture of equipotent R- and S-enantiomers. Fluoxetine metabolism involves CYP2D6 and CYP2C9 in the formation of its major metabolite, norfluoxetine. This metabolite is also present as two enantiomers, of which only the S-enantiomer exhibits comparable antidepressant activity. This study was conducted to assess the potential for an effect of alosetron on the pharmacokinetics of fluoxetine. This was an open-label, two-period, nonrandomized, crossover study in 12 healthy female and male volunteers. The pharmacokinetics for both enantiomers of fluoxetine and norfluoxetine were examined following single oral doses of 20 mg fluoxetine, given alone and in combination with alosetron 1 mg twice daily for 15 days. The results showed small delays in peak concentration but no clinically significant effect of alosetron on the pharmacokinetics of S- and R-fluoxetine or S- and R-norfluoxetine. Coadministration of alosetron and fluoxetine was well tolerated by all subjects.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Alosetron	Cytochrome P450 2C9	Protein	Humans	No	Substrate	Details