Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study

Wiebe, Sabrina; Schnell, David; Külzer, Raimund; Gansser, Dietmar; Weber, Anne; Wallenstein, Gudrun; Halabi, Atef; Conrad, Anja; Wind, Sven

doi:10.1007/s13318-016-0359-9

Cited by 24Pharmacogenetics and Drug MetabolismLung Cancer Treatments and MutationsAntibiotics Pharmacokinetics and Efficacy

Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study

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Wiebe, Sabrina, Schnell, David, Külzer, Raimund, Gansser, Dietmar, Weber, Anne, Wallenstein, Gudrun, Halabi, Atef, Conrad, Anja +1 more·2017·European Journal of Drug Metabolism and Pharmacokinetics

DOI 10.1007/s13318-016-0359-9PMC PMC5423921

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Abstract

Afatinib is an oral irreversible ErbB-Family Blocker indicated for treatment of patients with EGFR mutation positive advanced non-small cell lung cancer. This trial assessed whether renal impairment influences the pharmacokinetics and safety of afatinib. This was an open-label, single-dose study. Pharmacokinetic parameters after afatinib 40 mg were investigated in subjects with moderate (n = 8) or severe (n = 8) renal impairment (estimated glomerular filtration rate 30–59 mL/min/1.73 m2 and 15–29 mL/min/1.73 m2, respectively) and healthy matched controls (n = 14). Plasma and urine samples were collected before and up to 14 days after dosing for pharmacokinetic and plasma protein-binding assessment. Primary endpoints were area under the plasma concentration–time curve from time zero to the last quantifiable concentration (AUClast) and maximum plasma concentration (C max) between subjects with renal impairment and healthy matched controls. Pharmacokinetic profiles and plasma protein binding were similar in all groups. The extent of exposure, as indicated by AUClast and C max, was generally similar between the matched treatment groups, with the exception of the geometric mean ratio of AUClast for subjects with severe renal impairment, which showed a trend towards a higher value compared with matched healthy subjects (150.0 % [90 % CI 105.3–213.7]) Inter-individual variability was moderate (geometric mean coefficient of variation 28–39 % for moderate impairment, 34–42 % for severe impairment). Afatinib was well tolerated and urinary excretion was minimal. Moderate-to-severe renal impairment had a minor influence on the pharmacokinetics of afatinib that was within the observed inter-individual variability, suggesting that afatinib treatment can be considered in this patient population. Registered at ClinicalTrials.gov as NCT02096718.

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Moderate-to-severe renal impairment has a minor influence on afatinib pharmacokinetics.
“Moderate-to-severe renal impairment has been shown to have a minor influence on afatinib pharmacokinetics.”
From Afatinib for the treatment of EGFR mutation-positive NSCLC: A review of clinical findings (2020) · cites this paper as [59]

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Population pharmacokinetics of afatinib and exposure-safety relationships in Japanese patients with EGFR mutation-positive non-small cell lung cancer
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Authors: Wiebe, S., Schnell, D., Külzer, R., Gansser, D., Weber, A., Wallenstein, G., Halabi, A., Conrad, A., & Wind, S.
Affiliations: Boehringer Ingelheim (Germany) (DE)
Corresponding author: Wiebe, Sabrina
ORCID: Wiebe, Sabrina
Halabi, Atef
Wind, Sven
Venue: European Journal of Drug Metabolism and Pharmacokinetics
Publisher: Springer Science and Business Media LLC
Published: 2016-07-19
Volume: 42
Issue: 3
Pages: 461-469
ISSN: 0378-7966 (ISSN-L)
2107-0180
DOI: 10.1007/s13318-016-0359-9
PMC: PMC5423921
OpenAlex: W2488685184
Cited by: 24
References: 13
Citations by year: 2026: 1 · 2025: 3 · 2024: 2 · 2023: 4 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 2
FWCI: 3.35
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc
creativecommons.org/licenses/by-nc/4.0 (unspecified)
Locations: European Journal of Drug Metabolism and Pharmacokinetics (publishedVersion, cc-by-nc)
Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
PubMed Central (publishedVersion, cc-by-nc)
PubMed (publishedVersion)
Funders: Boehringer Ingelheim
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
Health Sciences › Medicine › Pharmacology › Antibiotics Pharmacokinetics and Efficacy
Keywords: afatinib, renal dysfunction, pharmacokinetics, EGFR mutation, non-small cell lung cancer, plasma protein binding, urinary excretion, interindividual variability, dose adjustment
MeSH terms: Afatinib, Aged, Carcinoma, Non-Small-Cell Lung, Female, Humans, Lung Neoplasms, Male, Middle Aged, Quinazolines, Case-Control Studies, Area Under Curve, Renal Insufficiency

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Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study

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