Afatinib pharmacokinetics and metabolism after oral administration to healthy male volunteers.

Summary of "Afatinib pharmacokinetics and metabolism after oral administration to healthy male volunteers."

To investigate the pharmacokinetics, metabolism and tolerability of afatinib (BIBW 2992), an oral irreversible ErbB family blocker, in healthy male volunteers.
In this open-label, single-center study, 8 healthy male volunteers received a single oral dose of 15 mg [(14)C]-radiolabeled afatinib (equivalent to 22.2 mg of the dimaleinate salt) as a solution. Blood, urine and fecal samples were collected for at least 96 hours (h) after dosing. Plasma and urine concentrations of afatinib were analyzed using high-performance liquid chromatography-tandem mass spectrometry. [(14)C]-radioactivity levels in plasma, whole blood, urine and feces were measured by liquid scintillation counting methods. Metabolite patterns were assessed by high-performance liquid chromatography.
[(14)C]-radioactivity was mainly excreted via feces (85.4%). Overall recovery of [(14)C]-radioactivity was 89.5%, indicative of a complete mass balance. Afatinib was slowly absorbed, with maximum plasma concentrations achieved at a median of 6 h after dosing, declining thereafter in a biexponential manner. The geometric mean terminal half-life of afatinib was 33.9 h in plasma and longer for [(14)C]-radioactivity in plasma and whole blood. Apparent total body clearance for afatinib was high (geometric mean 1,530 mL/min). The high volume of distribution (4,500 L) in plasma may indicate a high tissue distribution. Afatinib was metabolized to only a minor extent, with the main metabolite afatinib covalently bound to plasma proteins. Oxidative metabolism mediated via cytochrome P-450 was of negligible importance for the elimination of afatinib. Afatinib was well tolerated.
Afatinib displayed a complete mass balance with the main route of excretion via feces. Afatinib undergoes minimal metabolism.


Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse, 88400, Biberach an der Riss, Germany,

Journal Details

This article was published in the following journal.

Name: Cancer chemotherapy and pharmacology
ISSN: 1432-0843


DeepDyve research library

PubMed Articles [18949 Associated PubMed Articles listed on BioPortfolio]

Pharmacokinetics and pharmacodynamics of prasugrel in healthy Japanese subjects.

This randomized double-blind and placebo-controlled study assessed the pharmacodynamics and pharmacokinetics of prasugrel in healthy adult Japanese male subjects after single (n = 50) and multiple (...

Pharmacokinetics and Safety of a Single Dose of the Novel Necrosis Inhibitor LC28-0126 in Healthy Male Subjects.

A novel necrosis inhibitor, LC28-0126, is expected to have a cellular protective effect from ischaemic reperfusion injury in acute myocardial infarction. The objective of this study was to investigate...

Pharmacokinetics of voriconazole after intravenous and oral administration to healthy cats.

OBJECTIVE To determine pharmacokinetics and adverse effects after voriconazole administration to cats and identify an oral dose of voriconazole for cats that maintains plasma drug concentrations withi...

Pharmacokinetics of meloxicam after intramuscular and oral administration of a single dose to American flamingos (Phoenicopertus ruber).

OBJECTIVE To determine pharmacokinetics after IM and oral administration of a single dose of meloxicam to American flamingos (Phoenicopertus ruber). ANIMALS 14 adult flamingos. PROCEDURES Flamingos we...

Lack of Effect of Oral Cabotegravir on the Pharmacokinetics of a Levonorgestrel/Ethinyl Estradiol-Containing Oral Contraceptive in Healthy Adult Females.

This study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of HIV-1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) ...

Clinical Trials [9966 Associated Clinical Trials listed on BioPortfolio]

Absorption, Metabolism and Excretion of [14C]-Lasmiditan - Single Oral Dose Administration

This study will be an open-label, nonrandomized, absorption, metabolism, and excretion study of [14C]-lasmiditan administered as a 200-mg (approximately 100 µCi) oral solution to 8 health...

Absorption, Metabolism and Excretion (AME) of Single Dose Radiolabeled BVD-523 in Volunteers

The primary objective of this study is to characterize the metabolic disposition, pharmacokinetics (PK), and routes of elimination of [14C]‑labeled BVD‑523 after administration of a si...

Pharmacokinetics and Metabolism Study of Radiolabeled BMS-986142 in Healthy Male Subjects

This is an open-label, single-dose, study in healthy males. The primary objective is to assess the pharmacokinetics (PK), metabolism, and routes of elimination of a single oral dose of rad...

Pharmacokinetics and Metabolism of [14C]BMS-986165 in Healthy Male Participants

An oral dose in healthy subjects to obtain information about the absorption, metabolism, and excretion (AME) of BMS-986165

A Study Investigating the Excretion Balance, Pharmacokinetics and Metabolism of a Single Oral Dose of [14C]-Labeled RO7034067 in Healthy Male Participants

This is an open-label, non-randomized study investigating the excretion balance, PK and metabolism of a single oral dose of [14C]-labeled RO7034067 in healthy male participants. This study...

Medical and Biotech [MESH] Definitions

Agents that aid or increase the action of the principle drug (DRUG SYNERGISM) or that affect the absorption, mechanism of action, metabolism, or excretion of the primary drug (PHARMACOKINETICS) in such a way as to enhance its effects.

The giving of drugs, chemicals, or other substances by mouth.

Hard or soft soluble containers used for the oral administration of medicine.

MYCOBACTERIUM infections of the male reproductive tract (GENITALIA, MALE).

Pathological processes involving the male reproductive tract (GENITALIA, MALE).

Quick Search

DeepDyve research library

Relevant Topics

Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...

Gilotrif (afatinib)
GILOTRIF (afatinib) is a kinase inhibitor indicated for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L8...

Searches Linking to this Article