Effect of Ondansetron on Metformin Pharmacokinetics and Response in Healthy Subjects

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Qing LiYan Shu

Abstract

The 5-hydroxytryptamine-3 (5-HT3) receptor antagonists such as ondansetron have been used to prevent and treat nausea and vomiting for over 2 decades. This study was to determine whether ondansetron could serve as a perpetrator drug causing transporter-mediated drug-drug interactions in humans. Twelve unrelated male healthy Chinese volunteers were enrolled into a prospective, randomized, double-blind, crossover study to investigate the effects of ondansetron or placebo on the pharmacokinetics of and the response to metformin, a well-characterized substrate of organic cation transporters and multidrug and toxin extrusions (MATEs). Ondansetron treatment caused a statistically significantly higher Cmax of metformin compared with placebo (18.3 ± 5.05 versus 15.2 ± 3.23; P = 0.006) and apparently decreased the renal clearance of metformin by 37% as compared with placebo (P = 0.001). Interestingly, ondansetron treatment also statistically significantly improved glucose tolerance in subjects, as indicated by the smaller glucose area under the curve in the oral glucose tolerance test (10.4 ± 1.43) as compared with placebo (11.5 ± 2.29 mmol∙mg/l) (P = 0.020). It remains possible that ondansetron itself may affect glucose homeostasis in ...Continue Reading

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Citations

Jan 4, 2019·Clinical Pharmacology in Drug Development·Taylor ChoiShyeilla V Dhuria
Dec 13, 2018·Journal of Pharmacological Sciences·Jiagen WenWei Zhang
Jul 3, 2021·International Journal of Molecular Sciences·Blessy GeorgeLauren M Aleksunes
Sep 4, 2021·Cancer Chemotherapy and Pharmacology·Ken OgasawaraGopal Krishna

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