ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Influence of polymorphic OATP1B-type carriers on the disposition of docetaxel.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 91 citations in OpenAlex.
- Abundance of Hepatic Transporters in Caucasians: A Meta-Analysis.Drug metabolism and disposition: the biological fate of chemicals · 2016Pooled it
- Effects of prednisone on docetaxel pharmacokinetics in men with metastatic prostate cancer: A randomized drug-drug interaction study.British journal of clinical pharmacology · 2019Trial
- 4β-hydroxycholesterol as an endogenous CYP3A marker in cancer patients treated with taxanes.British journal of clinical pharmacology · 2015Trial
- Ribociclib is not a substrate or inhibitor of Oatp1b-mediated uptake in vivo.Cancer chemotherapy and pharmacology · 2026Article
- Role of solute carrier transporters in the biodistribution and toxicity of chemotherapeutic drugs.Pharmacological reviews · 2026Review
- Drug-Drug Interaction Liabilities with BTK Inhibitor TL-895.Cancer research communications · 2025Article
- Coproporphyrin I as an in vitro fluorescent probe to measure OATP1B1 transport activity.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Targeting a xenobiotic transporter to ameliorate vincristine-induced sensory neuropathy.JCI insight · 2023Article
- A Metabolomics Approach for Predicting OATP1B-Type Transporter-Mediated Drug-Drug Interaction Liabilities.Pharmaceutics · 2022Article
- Solute Carrier Transportome in Chemotherapy-Induced Adverse Drug Reactions.Reviews of physiology, biochemistry and pharmacology · 2022Article
- Pharmacogenetics of Breast Cancer Treatments: A Sub-Saharan Africa Perspective.Pharmacogenomics and personalized medicine · 2022Review
- The Effect of Single Nucleotide Variations in the Transmembrane Domain of OATP1B1 on in vitro Functionality.Pharmaceutical research · 2021Article
- Regulation of OATP1B1 Function by Tyrosine Kinase-mediated Phosphorylation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Investigating the influence of relevant pharmacogenetic variants on the pharmacokinetics and pharmacodynamics of orally administered docetaxel combined with ritonavir.The pharmacogenomics journal · 2021Article
- Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Article
- Role for Drug Transporters in Chemotherapy-Induced Peripheral Neuropathy.Clinical and translational science · 2021Review
- Exploring pharmacogenetics of paclitaxel- and docetaxel-induced peripheral neuropathy by evaluating the direct pharmacogenetic-pharmacokinetic and pharmacokinetic-neuropathy relationships.Expert opinion on drug metabolism & toxicology · 2021Review
- Review
- OATP1A/1B, CYP3A, ABCB1, and ABCG2 limit oral availability of the NTRK inhibitor larotrectinib, while ABCB1 and ABCG2 also restrict its brain accumulation.British journal of pharmacology · 2020Article
- Novel insights into the organic solute transporter alpha/beta, OSTα/β: From the bench to the bedside.Pharmacology & therapeutics · 2020Review
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
Abstract
purposeDocetaxel is extensively metabolized by CYP3A4 in the liver but mechanisms by which the drug is taken up into hepatocytes remain poorly understood. We hypothesized that (i) liver uptake of docetaxel is mediated by the polymorphic solute carriers OATP1B1 and OATP1B3 and (ii) inherited genetic defects in this process may impair systemic drug elimination. EXPERIMENTAL
designTransport of docetaxel was studied in vitro using various cell lines stably transfected with OATP1B1*1A (wild-type), OATP1B1*5 [c.521T>C (V174A); rs4149056], OATP1B3, or the mouse transporter Oatp1b2. Docetaxel clearance was evaluated in wild-type and Oatp1b2-knockout mice as well as in two cohorts of patients with multiple variant transporter genotypes (n = 213).
resultsDocetaxel was found to be a substrate for OATP1B1, OATP1B3, and Oatp1b2 but was not transported by OATP1B1*5. Deficiency of Oatp1b2 in mice was associated with an 18-fold decrease in docetaxel clearance (P = 0.0099), which was unrelated to changes in intrinsic metabolic capacity in mouse liver microsomes. In patients, however, none of the studied common reduced function variants in OATP1B1 or OATP1B3 were associated with docetaxel clearance (P > 0.05).
conclusionsThe existence of at least two potentially redundant uptake transporters in the human liver with similar affinity for docetaxel supports the possibility that functional defects in both of these proteins may be required to confer substantially altered disposition phenotypes. In view of the established exposure-toxicity relationships for docetaxel, we suggest that caution is warranted if docetaxel has to be administered together with agents that potently inhibit both OATP1B1 and OATP1B3.
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Registered trials
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.