Evidence map›Paper›PMID 29381826›Full record

ArticleBritish journal of clinical pharmacology2018

The effect of itraconazole and rifampicin on the pharmacokinetics of osimertinib.

Karthick Vishwanathan, Paul A Dickinson, Karen So, Karen Thomas, Yuh-Min Chen, Javier De Castro Carpeño, Anne-Marie C Dingemans, Hye Ryun Kim, Joo-Hang Kim, Matthew G Krebs and 4 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase I
In one paragraph

Article in British journal of clinical pharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 43 papers.

0numbers the graph read from it
0cells of the map it votes in
43citing papers in PubMed
5.3field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

NCT02157883 phase1completednot on this map

A Phase I, Open-label, Non-randomised Study to Assess the Effect of Itraconazole (a CYP3A4 Inhibitor) on the Pharmacokinetics of a Single Oral Dose of AZD9291 in Patients With EGFRm Positive NSCLC Whose Disease Has Progressed on an EGFR TKI

TypeinterventionalSponsorAstraZenecaRan2014 to 2023Enrolled39ConditionsAdvanced Non Small Cell Lung Cancer, Advanced (Inoperable) Non Small Cell Lung CancerArmsPharmacokinetic sampling, AZD9291, Itraconazole
NCT02197247 phase1completednot on this map

A Phase I, Open-Label, Non-Randomised, Multicentre Study to Assess the Effect of Rifampicin (a CYP3A4 Inducer) on the Pharmacokinetics of AZD9291 in Patients With EGFRm Positive NSCLC Whose Disease Has Progressed on an EGFR TKI

TypeinterventionalSponsorAstraZenecaRan2014 to 2021Enrolled41ConditionsNon Small Cell Lung CancerArmsPharmacokinetic sampling - AZD9291, Rifampicin, AZD9291 tablet dosing, Pharmacokinetic sampling - rifampicin, Pharmacokinetic sampling - AZ5140 and AZ7550
3 · Its place in the literature

Who cites it

43 citing papers in PubMed, 74 citations in OpenAlex.

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  18. Repurposing antifungal drugs for cancer therapy.Journal of advanced research · 2023
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 12 institutions in 8 countries.

Karthick VishwanathanQuantitative Clinical Pharmacology, AstraZeneca, Waltham, MA, USA.ORCID 0000-0002-6555-8131
Paul A DickinsonSeda Pharmaceutical Development Services, Alderley Edge, UK.
Karen SoGlobal Medicines Development / Global Clinical Development, AstraZeneca, Cambridge, UK.
Karen ThomasBiostatistics and Informatics, AstraZeneca, Macclesfield, UK.
Yuh-Min ChenDepartment of Chest Medicine, Taipei Veterans General Hospital, and School of Medicine, National Yang-Ming Medical University, Taipei, Taiwan.
Javier De Castro CarpeñoHospital Universitario La Paz, Madrid, Spain.
Anne-Marie C DingemansDepartment of Respiratory Disease, Maastricht University Medical Center, Maastricht, Netherlands.
Hye Ryun KimYonsei Cancer Center, Division of Medical Oncology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
Joo-Hang KimCHA Bungdang Medical Center, CHA University, Gyeonggi-do, Republic of Korea.
Matthew G KrebsThe Christie NHS Foundation Trust, Manchester UK and Division of Molecular and Clinical Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.
James Chih-Hsin YangNational Taiwan University Hospital, Taipei, Taiwan.
Khanh BuiQuantitative Clinical Pharmacology, AstraZeneca, Waltham, MA, USA.
Doris WeilertIQVIA™, Overland Park, KS, USA.
R Donald HarveyWinship Cancer Institute of Emory University, Atlanta, GA, USA.
AstraZeneca (South Korea) · KRAstraZeneca (United Kingdom) · GBCHA University Bundang Medical Center · KREmory University · USHospital Universitario La Paz · ESIQVIA (United States) · USMaastricht University Medical Centre · NLManchester Academic Health Science Centre · GBNational Taiwan University Hospital · TWNational Yang Ming Chiao Tung University · TWPixelMill (United Kingdom) · GBYonsei University · KR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsWe investigated the effects of a strong CYP3A4 inhibitor (itraconazole) or inducer (rifampicin) on the pharmacokinetics of the epidermal growth factor receptor-tyrosine kinase inhibitor osimertinib, in patients with advanced non-small cell lung cancer in two Phase I, open-label, two-part clinical studies. Part one of both studies is reported.

methodsIn the itraconazole study (NCT02157883), patients received single-dose osimertinib 80 mg on Days 1 and 10 and itraconazole (200 mg twice daily) on Days 6-18 orally. In the rifampicin study (NCT02197247), patients received osimertinib 80 mg once daily on Days 1-77 and rifampicin 600 mg once daily on Days 29-49.

resultsIn the itraconazole study (n = 36), the geometric least squares mean (GMLSM) ratios (osimertinib plus itraconazole/osimertinib alone) for C

conclusionsOsimertinib can be co-administered with CYP3A4 inhibitors, but strong CYP3A inducers should be avoided if possible.

Indexed as

AcrylamidesAdministration, OralAdultAgedAged, 80 and overAniline CompoundsAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCytochrome P-450 CYP3A InducersCytochrome P-450 CYP3A InhibitorsDrug Administration ScheduleDrug InteractionsFemaleHumansIndolesItraconazoleAcrylamidesAniline CompoundsAntineoplastic AgentsCytochrome P-450 CYP3A InducersCytochrome P-450 CYP3A InhibitorsIndolesItraconazoleosimertinibPiperazinesProtein Kinase InhibitorsPyrimidinesRifampinclinical pharmacology, drug metabolismdrug analysis, lung cancerdrug informationdrug interactionsoncologypharmacokinetics, biomarkers

Identifiers

PMID29381826
PMCPMC5980546
OpenAlexW2793612529

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.