ArticleThe pharmacogenomics journal2012
Effects of OCT1 polymorphisms on the cellular uptake, plasma concentrations and efficacy of the 5-HT(3) antagonists tropisetron and ondansetron.
Article in The pharmacogenomics journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.
- Variants in Pharmacokinetic Transporters and Glycemic Response to Metformin: A Metgen Meta-Analysis.Clinical pharmacology and therapeutics · 2017Pooled it
- Population Pharmacokinetic Model of Platinum Disposition in Cancer Patients Receiving Cisplatin and Randomized to 5-HTJournal of clinical pharmacology · 2025Trial
- A randomized trial evaluating the association between related gene polymorphism and nausea and vomiting induced by cisplatin multi-day chemotherapy.BMC medical genomics · 2023Trial
- Effect of Ondansetron on Metformin Pharmacokinetics and Response in Healthy Subjects.Drug metabolism and disposition: the biological fate of chemicals · 2016Trial
- Endogenous glucose production increases in response to metformin treatment in the glycogen-depleted state in humans: a randomised trial.Diabetologia · 2015Trial
- Genetically Determined Loss-of-Function of the Organic Cation Transporter OCT1 Is Associated with Lower Liver Fat Content in Humans.International journal of molecular sciences · 2026Article
- Feed-Forward Deep Neural Networks Predict Substrate-Specific Effects of Transporter Variants to Explain Drug Response Variability.Clinical and translational science · 2026Article
- Substrate-specific inhibition of organic cation transporter 1 revealed using a multisubstrate drug cocktail.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Effect of SLC22A1 polymorphism on the pharmacokinetics of proguanil in Korean: A semi-physiologic population pharmacokinetic approach.Clinical and translational science · 2024Article
- The Competitive Counterflow Assay for Identifying Drugs Transported by Solute Carriers: Principle, Applications, Challenges/Limits, and Perspectives.European journal of drug metabolism and pharmacokinetics · 2024Review
- Modulating the Activity of the Human Organic Cation Transporter 2 Emerges as a Potential Strategy to Mitigate Unwanted Toxicities Associated with Cisplatin Chemotherapy.International journal of molecular sciences · 2024Article
- Role of Drug Transporters in Elucidating Inter-Individual Variability in Pediatric Chemotherapy-Related Toxicities and Response.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Guide to development of compound files for PBPK modeling in the Simcyp population-based simulator.CPT: pharmacometrics & systems pharmacology · 2022Article
- Amino acids in transmembrane helix 1 confer major functional differences between human and mouse orthologs of the polyspecific membrane transporter OCT1.The Journal of biological chemistry · 2022Article
- Cloning and Functional Characterization of Dog OCT1 and OCT2: Another Step in Exploring Species Differences in Organic Cation Transporters.International journal of molecular sciences · 2022Article
- No significant influence of OCT1 genotypes on the pharmacokinetics of morphine in adult surgical patients.Basic & clinical pharmacology & toxicology · 2022Article
- Article
- Drug-Drug Interactions in Vestibular Diseases, Clinical Problems, and Medico-Legal Implications.International journal of environmental research and public health · 2021Review
- Tapping into 5-HTInternational journal of molecular sciences · 2021Review
- Pharmacogenomics in cancer supportive care: key issues and future directions.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2021Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
After uptake into liver cells, the antiemetic drugs tropisetron and ondansetron undergo metabolic inactivation by cytochrome P450 2D6 (CYP2D6). We investigated whether the hepatic organic cation transporter 1 (OCT1; SLC22A1) mediates cellular uptake and whether common OCT1 loss-of-function polymorphisms affect pharmacokinetics and efficacy of both drugs. Both tropisetron and ondansetron inhibited ASP(+) uptake in OCT1-overexpressing HEK293 cells. Overexpression of wild-type, but not OCT1 loss-of-function variants, significantly increased tropisetron uptake. Correspondingly, patients with two loss-of-function OCT1 alleles had higher tropisetron plasma concentrations (n=59, P<0.04) and higher clinical efficacy (n=91, P=0.009) compared with carriers of fully active OCT1. Overexpression of OCT1 did not increase ondansetron uptake. Nevertheless, OCT1 genotypes correlated with pharmacokinetics (n=45, P<0.05) and clinical efficacy (n=222, P<0.02) of ondansetron, the effect size of OCT1 genotypes on pharmacokinetics and efficacy was greater for tropisetron than for ondansetron. In conclusion, in addition to the known effects of CYP2D6, OCT1 deficiency may increase efficacy of tropisetron and potentially of ondansetron by limiting their hepatic uptake.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.