Trial reportBritish journal of clinical pharmacology2009
Gefitinib-phenytoin interaction is not correlated with the C-erythromycin breath test in healthy male volunteers.
Trial report in British journal of clinical pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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
14 citing papers in PubMed.
- OATP1B1 polymorphism as a determinant of erythromycin disposition.Clinical pharmacology and therapeutics · 2012Trial
- Busting the Breast Cancer with AstraZeneca's Gefitinib.Advances in pharmacological and pharmaceutical sciences · 2023Review
- A Prospective Study of Medication Surveillance of a Pediatric Tertiary Care Hospital in Lahore, Pakistan.Pediatric reports · 2022Article
- Pharmacokinetic properties and bioequivalence of gefitinib 250 mg in healthy Korean male subjects.Translational and clinical pharmacology · 2021Article
- Optimising Seniors' Metabolism of Medications and Avoiding Adverse Drug Events Using Data on How Metabolism by Their P450 Enzymes Varies with Ancestry and Drug-Drug and Drug-Drug-Gene Interactions.Journal of personalized medicine · 2020Article
- Long-term safety of icotinib in patients with non-small cell lung cancer: a retrospective, real-world study.Journal of thoracic disease · 2020Article
- Comparative review of drug-drug interactions with epidermal growth factor receptor tyrosine kinase inhibitors for the treatment of non-small-cell lung cancer.OncoTargets and therapy · 2019Review
- Drug-Drug Interactions, Safety, and Pharmacokinetics of EGFR Tyrosine Kinase Inhibitors for the Treatment of Non-Small Cell Lung Cancer.Journal of the advanced practitioner in oncology · 2018Review
- Effects of polymorphisms in CYP2D6 and ABC transporters and side effects induced by gefitinib on the pharmacokinetics of the gefitinib metabolite, O-desmethyl gefitinib.Medical oncology (Northwood, London, England) · 2016Article
- Observation of hepatotoxicity during long-term gefitinib administration in patients with non-small-cell lung cancer.Anti-cancer drugs · 2016Observational
- Metabolism-related pharmacokinetic drug-drug interactions with tyrosine kinase inhibitors: current understanding, challenges and recommendations.British journal of clinical pharmacology · 2015Review
- Pharmacokinetic interaction between ivabradine and phenytoin in healthy subjects.Clinical drug investigation · 2012Article
- Clinical pharmacokinetics of tyrosine kinase inhibitors: focus on 4-anilinoquinazolines.Clinical pharmacokinetics · 2011Review
- Communicating about potential drug harms: safety implications for patients.British journal of clinical pharmacology · 2009Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsWe aimed to describe the pharmacokinetic interaction between phenytoin, a potent CYP3A4 and P-glycoprotein (P-gp) (ABCB1) inducer, and gefitinib, a CYP3A4, CYP2D6 and P-gp substrate.
methodsAn open-label, randomized, two-phase crossover study was conducted. Eighteen healthy male volunteers (nine homozygous CC and nine homozygous TT as determined by their ABCB1 C3435T polymorphism in exon 26) received a single oral dose of 250 mg gefitinib alone or after 5 days treatment with phenytoin (5 mg kg(-1) daily). Gefitinib plasma concentrations were determined by high-performance liquid chromatography. Hepatic CYP3A4 activity was evaluated by the (14)C-erythromycin breath test (ERMBT) and the ABCB1 and CYP2D6 genetic polymorphisms were determined by the TaqMan allelic discrimination assay and long polymerase chain reaction, respectively.
resultsFollowing treatment with phenytoin, mean gefitinib C(max) and AUC(0-infinity) decreased by 26 +/- 44% [95% confidence interval (CI) for the difference 5-48%, P= 0.005] and 47 +/- 26% (95% CI for the difference 34-60%, P= 0.001), respectively, and apparent oral clearance increased by 126 +/- 93% (95% CI for the difference 80-172%, P= 0.004). Concomitantly, phenytoin increased the mean ERMBT by 91 +/- 44% (95% CI 75-105%, P < 0.001) from baseline, but the extent of liver CYP3A4 induction was not correlated to the extent of interaction. Furthermore, this interaction was independent of ABCB1 genetic polymorphism. The CYP2D6 genotype was slightly but significantly related to gefitinib clearance (P= 0.04) during the control phase.
conclusionsThe significant interaction between gefitinib and phenytoin was not correlated with the erythromycin breath test and was independent of ABCB1 polymorphism, but may involve presystemic CYP3A-mediated intestinal first-pass.
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