ArticleClinical pharmacology and therapeutics2008
Pharmacogenetic pathway analysis of irinotecan.
Article in Clinical pharmacology and therapeutics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Serum metabolic traits reveal therapeutic toxicities and responses of neoadjuvant chemoradiotherapy in patients with rectal cancer.Nature communications · 2022Trial
- Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided byJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2020Trial
- Phenotyping of UGT1A1 Activity Using Raltegravir Predicts Pharmacokinetics and Toxicity of Irinotecan in FOLFIRI.PloS one · 2016Trial
- Quantification of the impact of enzyme-inducing antiepileptic drugs on irinotecan pharmacokinetics and SN-38 exposure.Journal of clinical pharmacology · 2015Trial
- Population Pharmacokinetic Modeling of the Enterohepatic Recirculation of Fimasartan in Rats, Dogs, and Humans.The AAPS journal · 2015Trial
- Flavopiridol pharmacogenetics: clinical and functional evidence for the role of SLCO1B1/OATP1B1 in flavopiridol disposition.PloS one · 2010Trial
- Pharmacokinetic Simulation and Area under the Curve Estimation of Drugs Subject to Enterohepatic Circulation.Pharmaceutics · 2024Article
- Phase 1 study of sorafenib and irinotecan in pediatric patients with relapsed or refractory solid tumors.Pediatric blood & cancer · 2021Article
- Article
- Effect of UGT1A1, CYP3A and CES Activities on the Pharmacokinetics of Irinotecan and its Metabolites in Patients with UGT1A1 Gene Polymorphisms.European journal of drug metabolism and pharmacokinetics · 2021Article
- Pharmacogenomics meets precision cardio-oncology: is there synergistic potential?Human molecular genetics · 2020Review
- Population pharmacokinetic model of irinotecan and its metabolites in patients with metastatic colorectal cancer.European journal of clinical pharmacology · 2019Article
- Pharmacogenetics of toxicity of 5-fluorouracil, doxorubicin and cyclophosphamide chemotherapy in breast cancer patients.Oncotarget · 2018Article
- Improved Progression-Free Survival in Irinotecan-Treated Metastatic Colorectal Cancer Patients Carrying the HNF1A Coding Variant p.I27L.Frontiers in pharmacology · 2017Article
- Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer.Journal of clinical pharmacology · 2016Article
- Clinical validity of new genetic biomarkers of irinotecan neutropenia: an independent replication study.The pharmacogenomics journal · 2016Article
- Effect of MRP2 and MRP3 Polymorphisms on Anastrozole Glucuronidation and MRP2 and MRP3 Gene Expression in Normal Liver Samples.International journal of cancer research and molecular mechanisms · 2015Article
- Article
- ABCC2 polymorphisms and haplotype are associated with drug resistance in Chinese epileptic patients.CNS neuroscience & therapeutics · 2012Article
- Functional analysis of nonsynonymous single nucleotide polymorphisms of multidrug resistance-associated protein 2 (ABCC2).Pharmacogenetics and genomics · 2011Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Irinotecan, a chemotherapeutic agent against various solid tumors, is a prodrug requiring activation to SN-38. Irinotecan's complex pharmacokinetics potentially allow for many genetic sources of variability. We explored relationships between pharmacokinetic pathways and polymorphisms in genes associated with irinotecan's metabolism and transport. We fitted a seven-compartment pharmacokinetic model with enterohepatic recirculation (EHR) to concentrations of irinotecan and metabolites SN-38, SN-38 glucuronide (SN-38G), and aminopentanoic acid (APC). Principal component analysis (PCA) of patient-specific parameter estimates produced measures interpretable along pathways. Nine principal components provided good characterization of the overall variation. Polymorphisms in genes UGT1A1, UGT1A7, and UGT1A9 had strong associations with a component corresponding to the irinotecan-to-SN-38 pathway and SN-38 recirculation and to a component relating to SN-38-to-SN-38G conversion and elimination of SN-38G. The component characterizing irinotecan's compartments was associated with HNF1alpha and ABCC2 polymorphisms. The exploratory analysis with PCA in this pharmacogenetic analysis was able to identify known associations and may have allowed identification of previously uncharacterized functional polymorphisms.
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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.