ArticleClinical drug investigation2014
Effect of rifampicin on the pharmacokinetics of lenvatinib in healthy adults.
Article in Clinical drug investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Safety and efficacy profile of lenvatinib in cancer therapy: a systematic review and meta-analysis.Oncotarget · 2016Pooled it
- Influences of ABC transporter and CYP3A4/5 genetic polymorphisms on the pharmacokinetics of lenvatinib in Chinese healthy subjects.European journal of clinical pharmacology · 2020Trial
- Population pharmacokinetic analysis of lenvatinib in healthy subjects and patients with cancer.British journal of clinical pharmacology · 2016Trial
- ALBI Grade is a Determinant of Lenvatinib Pharmacokinetics, Efficacy, and Toxicities in Japanese Patients with Hepatocellular Carcinoma.Clinical pharmacokinetics · 2026Observational
- Development of a sensitive plasma lenvatinib quantification method and validation in thyroid cancer patients.Journal of the Endocrine Society · 2026Article
- High-performance PBPK model for predicting CYP3A4 induction-mediated drug interactions: a refined and validated approach.Frontiers in pharmacology · 2025Article
- Relevance of plasma lenvatinib concentrations and endogenous urinary cytochrome P450 3A activity biomarkers in clinical practice.Pharmacology research & perspectives · 2024Article
- Insights into lenvatinib resistance: mechanisms, potential biomarkers, and strategies to enhance sensitivity.Medical oncology (Northwood, London, England) · 2024Review
- Evaluation of the inhibitory effect of azoles on pharmacokinetics of lenvatinib in rats both in vivo and in vitro by UPLC-MS/MS.Thoracic cancer · 2023Article
- Differences in the pharmacokinetics and steady-state blood concentrations of orally administered lenvatinib in adult and juvenile rats.Frontiers in pharmacology · 2023Article
- Lenvatinib resistance mechanism and potential ways to conquer.Frontiers in pharmacology · 2023Review
- Involvement of Transporters in Intestinal Drug-Drug Interactions of Oral Targeted Anticancer Drugs Assessed by Changes in Drug Absorption Time.Pharmaceutics · 2022Article
- Pharmacokinetic Interactions between Canagliflozin and Sorafenib or Lenvatinib in Rats.Molecules (Basel, Switzerland) · 2022Article
- Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers.Cancers · 2022Review
- Influence of schisantherin A on the pharmacokinetics of lenvatinib in rats and its potential mechanism.Journal of gastrointestinal oncology · 2022Article
- Co-administration of MDR1 and BCRP or EGFR/PI3K inhibitors overcomes lenvatinib resistance in hepatocellular carcinoma.Frontiers in oncology · 2022Article
- Effects of rifampicin on the pharmacokinetics of alflutinib, a selective third-generation EGFR kinase inhibitor, and its metabolite AST5902 in healthy volunteers.Investigational new drugs · 2021Article
- Impact of Local Liver Irradiation Concurrent Versus Sequential with Lenvatinib on Pharmacokinetics and Biodistribution.Cancers · 2021Article
- A Review of CYP3A Drug-Drug Interaction Studies: Practical Guidelines for Patients Using Targeted Oral Anticancer Drugs.Frontiers in pharmacology · 2021Review
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
objectivesLenvatinib is an oral, multitargeted tyrosine kinase inhibitor under clinical investigation in solid tumours. This study evaluated the influence of P-glycoprotein (P-gp) inhibition (single-dose rifampicin) and simultaneous cytochrome P450 3A4 (CYP3A4)/P-gp induction (multiple-dose rifampicin) on lenvatinib pharmacokinetics.
methodsThis Phase I, single-centre, single-dose (lenvatinib mesylate 24 mg), open-label, sequential study enrolled 15 healthy volunteers. Three regimens were administered over three periods: Period (P) 1 (Days 1-8), P2 (Days 15-22) and P3 (Days 29-50), with a 14-day (first dose) and 28-day (second dose) washout period after lenvatinib mesylate administration (Day 1, Day 15 and Day 43). In P2, a single oral dose of rifampicin (600 mg) was coadministered with lenvatinib. In P3, rifampicin was administered daily (600 mg) for 21 days (Days 29-49). Serial blood samples were collected, and plasma concentrations of total (protein bound + unbound) and free (unbound) lenvatinib and total metabolites (M1, M2, M3 and M5) were measured by validated high-performance liquid chromatography/tandem mass spectrometry.
resultsSingle-dose rifampicin (P-gp inhibition) increased area under the plasma concentration-time curve from time zero to infinity (AUC0-∞) of free and total lenvatinib by 32 and 31 %, respectively. Multiple-dose rifampicin (simultaneous P-gp and CYP3A4 induction) decreased lenvatinib AUC0-∞ (total: 18 %; free: 9 %). Treatment-emergent adverse events were mild or moderate and occurred in 7 subjects (47 %).
conclusionLenvatinib exposure was increased by P-gp inhibition; however, based on free concentrations, simultaneous P-gp and CYP3A4 induction results met the prespecified bioequivalence 90 % confidence interval. Overall, the magnitude of these changes was relatively small, and likely not clinically meaningful.
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