# Serotonin-Transporter Polymorphism Influences Response to Alosetron (Lotronex)



## Jeffrey Roberts (Apr 15, 1987)

http://www.medscape.com/viewarticle/440940?mpid=3473 Serotonin-Transporter Polymorphism Influences Response to AlosetronBy Will Boggs, MD NEW YORK (Reuters Health) Sept 03 - A polymorphism in the promoter for the serotonin transporter protein (SERT) gene influences the effectiveness of alosetron, a serotonin receptor antagonist recently approved by FDA for the treatment of irritable bowel syndrome (IBS), according to a report in the August issue of the journal Gastroenterology. Alosetron has been shown to relieve IBS pain and to normalize bowel function in women with diarrhea-predominant IBS (D-IBS), the authors report, but similar benefits have not been apparent in men. Gender-related differences in pharmacokinetics failed to account for the differences in efficacy. Dr. Michael Camilleri and colleagues from Mayo Foundation in Rochester, Minnesota examined the influence of a 44-base-pair insertion in the promoter region of the SERT gene (SERT-P) on the response of colonic transit times to alosetron in 30 patients with D-IBS. Nine of 15 women and 3 of 15 men experienced a retardation of colonic transit time with alosetron treatment that met the preestablished efficacy criterion, the report indicates. Patients with long homozygous polymorphism were significantly more likely to experience a clinically meaningful slowing of colonic transit with alosetron than were patients with heterozygous or short homozygous polymorphism, the authors report. Colonic transit times did not differ did not differ between patients with short homozygous polymorphism and heterozygous patients, the results indicate. "This study leads to the hypothesis that people with long polymorphism may require a lower dose for the same clinical efficacy," Dr. Camilleri told Reuters Health. "If the opposite is confirmed in people with short polymorphism, it may be that the latter patients require a higher dose of medication." "One size does not fit all," concluded Dr. Camilleri. "Diversity in responsiveness may influence each individual's response to medication as well as the overall assessment of the efficacy of a drug in clinical trials. Pharmacogenomics need to be considered before writing off the potential benefits or adverse effects of novel medications." "We are unable to determine whether the greater efficacy with alosetron in women is related to the different SERT-P polymorphisms," the investigators add. "A separate study with a larger sample of IBS patients with diverse and well-characterized symptom phenotype is currently being conducted in our laboratory to assess the influence of SERT-P genotype on clinical manifestations of IBS." Gastroenterology 2002;123:425-432. --------------------------------------------------------------------------------Reuters Health Information 2002. ï¿½ 2002 Reuters Ltd.


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## IBS2 (Feb 7, 1999)

Jeff, Good article stating that lotronex should have it's does titrated to meet the individual need of the patient. Then again, tell us something we didn't know already.Regards,Tom


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