title: Influence of Renal Impairment on the Pharmacokinetics of Afatinib: An Open-Label, Single-Dose Study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 m2and 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 (Cmax) between subjects with renal impairment and healthy matched controls.
  
  
  RESULTS
  Pharmacokinetic profiles and plasma protein binding were similar in all groups. The extent of exposure, as indicated by AUClastand Cmax, was generally similar between the matched treatment groups, with the exception of the geometric mean ratio of AUClastfor 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany. sabrina.wiebe@boehringer-ingelheim.com.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Wiebe
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schnell
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
authors.forename: Raimund
authors.initials: R
authors.lastname: Külzer
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Gansser
authors.affiliation: Datamap GmbH, Freiburg im Breisgau, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Weber
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Wallenstein
authors.affiliation: Clinical Research Services (CRS) Kiel GmbH, Kiel, Germany.
authors.forename: Atef
authors.initials: A
authors.lastname: Halabi
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Conrad
authors.affiliation: Translational Medicine and Clinical Pharmacology, Boehringer Ingelheim Pharma GmbH & Co KG, Birkendorfer Strasse 65, 88397, Biberach an der Riss, Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Wind
mesh_terms: D000077716:Afatinib; D000368:Aged; D019540:Area Under Curve; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011799:Quinazolines / Q000493:pharmacokinetics* / Q000627:therapeutic use; D051437:Renal Insufficiency / Q000378:metabolism* / Q000503:physiopathology*
chemical_list: D011799:Quinazolines; D000077716:Afatinib