# Lotronex and fluoxetine



## eric (Jul 8, 1999)

FYI: J Clin Pharmacol 2001 Apr;41(4):455-8 Related Articles, Books Effect of alosetron on the pharmacokinetics of fluoxetine. D'Souza DL, Dimmitt DC, Robbins DK, Nezamis J, Simms L, Koch KM. Department of Clinical Pharmacology, Glaxo Wellcome Canada, Mississauga, Ontario. 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. PMID: 11304903 [PubMed - in process] ------------------Moderator of the Cognitive Behavioral Therapy, Anxiety and Hypnotherapy forumI work with Mike and the IBS Audio Program. www.ibshealth.com www.ibsaudioprogram.com


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## Kerri (Oct 1, 1999)

Eric,Please summarize that article in English. Thanks!Kerri


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## Kathleen M. (Nov 16, 1999)

The researchers were looking to determine if there was any drug interaction between the antidepressant fluoxetine (prozac) and alosetron (Lotronex).There is some possibility of their being an interaction because they are both metabolized by some of the same enzymes in the liver (P450 and the CYP##'s are some of the various versions of this type of enzyme).The prozac you take is a mixture of two chemcial that are mirror images of each other. They have the same # of all the same atoms, but they are arranged just a little bit differntly and that makes the mirror images of each other. This is important because alot of times only one of the two mirror images binds to whatever the chemical needs to bind to cause an effect. Many biologically active and organic molecules and many of the molecules in your body have this mirror image thing going on for instance with sugars and amino acids we only use one of the two mirror images of these molecules.With Prozac the two mirror images are in the pill in equal amounts in this case they are equipotent, so it sounds like both do the job. These two molecules are metabolized in the liver by some of the CYP## enzymes to form another compound called norfluoxetine each mirror image of the Prozac makes a different mirror image of the metabolite. The metabolites aren't equipotent, only one of the two has antidepressant activity.Now this could be important clinically because if the Lotronex messes up the metabolism of Prozac it could mean that someone gets either less of the active metabolites of Prozac or more of the active metabolites of Prozac, and many dangerous drug interactions occur because Drug A screws up the metabolism of Drug B and the patient either gets to much of Drug B running around which can be dangerous because higher does equal more side effects OR you now have less of Drug B running around and you don't have enough of Drug B to be effective and you risk having symptoms of whatever disease Drug B was treating.For the experiment they gave people 20 mgs of fluoxetine and 1 mg of alosetron 2X a day for 15 days. The measured the amounts of both mirror images of Prozac and both mirror images of the metabolite. There was a small delay in the peak concentrations, but not enough that would be clinically significant.Therefore if you take Prozac you can take Lotronex without having the Lotronex mess up the Prozac.K.------------------I have no financial, academic, or any other stake in any commercial product mentioned by me.My story and what worked for me in greatly easing my IBS: http://www.ibsgroup.org/ubb/Forum17/HTML/000015.html [This message has been edited by kmottus (edited 04-19-2001).]


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## Kerri (Oct 1, 1999)

Thanks K! They need to have "medicalese" as a foreign language in school







Kerri


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## Kathleen M. (Nov 16, 1999)

They doThe courses are called:Intro to BiologyIntro to ChemistryIntro to Physics.For the most part they are vocabulary courses with just enough algebra thrown in to convince people that they want to be psychology/sociology majors.K.------------------I have no financial, academic, or any other stake in any commercial product mentioned by me.My story and what worked for me in greatly easing my IBS: http://www.ibsgroup.org/ubb/Forum17/HTML/000015.html


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