Trial reportBritish journal of clinical pharmacology2011
Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects.
Trial report in British journal of clinical pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 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
18 citing papers in PubMed, 52 citations in OpenAlex.
- Multiple Administrations of Itraconazole Increase Plasma Exposure to Pyrotinib in Chinese Healthy Adults.Drug design, development and therapy · 2021Trial
- Pharmacokinetic drug-drug interaction between ethinyl estradiol and gestodene, administered as a transdermal fertility control patch, and two CYP3A4 inhibitors and a CYP3A4 substrate.European journal of drug metabolism and pharmacokinetics · 2015Trial
- Neratinib for HER2-positive breast cancer with an overlooked option.Molecular medicine (Cambridge, Mass.) · 2023Review
- A phase I trial of the pan-ERBB inhibitor neratinib combined with the MEK inhibitor trametinib in patients with advanced cancer with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation or KRAS mutation.Cancer chemotherapy and pharmacology · 2023Article
- The influence of verapamil on the pharmacokinetics of the pan-HER tyrosine kinase inhibitor neratinib in rats: the role of P-glycoprotein-mediated efflux.Investigational new drugs · 2023Article
- Involvement of Transporters in Intestinal Drug-Drug Interactions of Oral Targeted Anticancer Drugs Assessed by Changes in Drug Absorption Time.Pharmaceutics · 2022Article
- Neratinib causes non-recoverable gut injury and reduces intestinal cytochrome P450 3A enzyme in mice.Toxicology research · 2022Article
- Pivotal Considerations for Optimal Deployment of Healthy Volunteers in Oncology Drug Development.Clinical and translational science · 2020Review
- Oral oncolytic and antiretroviral therapy administration: dose adjustments, drug interactions, and other considerations for clinical use.Drugs in context · 2019Review
- Raman micro-spectroscopy monitors acquired resistance to targeted cancer therapy at the cellular level.Scientific reports · 2018Article
- Raman Microspectroscopic Evidence for the Metabolism of a Tyrosine Kinase Inhibitor, Neratinib, in Cancer Cells.Angewandte Chemie (International ed. in English) · 2018Article
- Neratinib: First Global Approval.Drugs · 2017Review
- Neratinib resistance and cross-resistance to other HER2-targeted drugs due to increased activity of metabolism enzyme cytochrome P4503A4.British journal of cancer · 2017Article
- LC-MS/MS assay for the quantitation of the tyrosine kinase inhibitor neratinib in human plasma.Journal of pharmaceutical and biomedical analysis · 2017Article
- The relevance of using 3D cell cultures, in addition to 2D monolayer cultures, when evaluating breast cancer drug sensitivity and resistance.Oncotarget · 2016Article
- Label-free LC-MS analysis of HER2+ breast cancer cell line response to HER2 inhibitor treatment.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2015Article
- Neratinib reverses ATP-binding cassette B1-mediated chemotherapeutic drug resistance in vitro, in vivo, and ex vivo.Molecular pharmacology · 2012Article
- Drug-drug interactions--bridging the gulf between the bench and the bedside?British journal of clinical pharmacology · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimThe primary objective was to evaluate the pharmacokinetics of a single dose of neratinib, a potent, low-molecular-weight, orally administered, irreversible pan-ErbB (ErbB-1, -2, -4) receptor tyrosine kinase inhibitor, during co-administration with ketoconazole, a potent CYP3A4 inhibitor.
methodsThis was an open-label, randomized, two-period, crossover study. Fasting healthy adults received a single oral dose of neratinib 240 mg alone and with multiple oral doses of ketoconazole 400 mg. Blood samples were collected up to 72 h after each neratinib dose. Plasma concentration data were analyzed using a noncompartmental method. The least square geometric mean ratios [90% confidence interval (CI)] of C(max) (neratinib+ketoconazole): C(max) (neratinib alone), and AUC(neratinib+ketoconazole): AUC(neratinib alone) were assessed.
resultsTwenty-four subjects were enrolled. Compared with neratinib administered alone, co-administration of ketoconazole increased neratinib C(max) by 3.2-fold (90% CI: 2.4, 4.3) and AUC by 4.8-fold (3.6, 6.5). Median t(max) was 6.0 h with both regimens. Ketoconazole decreased mean apparent oral clearance of neratinib from 346 lh(-1) to 87.1 lh(-1) and increased mean elimination half-life from 11.7 h to 18.0 h. The incidence of adverse events was comparable between the two regimens (50% neratinib alone, 65% co-administration with ketoconazole).
conclusionCo-administration of neratinib with ketoconazole, a potent CYP3A inhibitor, increased neratinib C(max) by 3.2-fold and AUC by 4.8-fold compared with administration of neratinib alone. These results indicate that neratinib is a substrate of CYP3A and is susceptible to interaction with potent CYP3A inhibitors and, thus, dose adjustments may be needed if neratinib is administered with such compounds.
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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.