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, Peter.Stopfer@boehringer-ingelheim.com.
This article was published in the following journal.
Name: Cancer chemotherapy and pharmacology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22200729
- DOI: http://dx.doi.org/10.1007/s00280-011-1803-9
Abstract 1. Few studies describing the pharmacokinetic properties of chlorogenic acid (CA) and corydaline (CRD) which are marker compounds of a new prokinetic botanical agent, DA-9701, have been re...
Afatinib is a potent, irreversible, ErbB family blocker in clinical development for the treatment of advanced non-small cell lung cancer, metastatic head and neck cancer, and other solid tumours. As a...
The growing interest in the composition and effects of microbiota raised the question how drug pharmacokinetics could be influenced by concomitant application of probiotics. The aim of this study was...
Abstract 1. The pharmacokinetics of danofloxacin was investigated in common pheasants, guinea fowls and Japanese quails after intravenous (i.v.) and oral (p.o.) administration at a dose of 10 mg kg-1...
The effect of silymarin (SMN) on the pharmacokinetics of atorvastatin in diabetic rats was evaluated. Male Wistar rats were assigned into two major groups and then sub-grouped according to the purpose...
The purpose of this study is to characterise the metabolism, excretion and pharmacokinetics of a single oral dose of [14C] AZD1236 in healthy male subjects.
The purpose of the study is to characterize the absorption, distribution, metabolism and excretion (ADME) of a single oral dose of [14C]AZD1981
To investigate the safety, tolerance, pharmacokinetics and pharmacodynamics of tolvaptan 15, 30 and 60 mg after single oral administration in healthy Korean male subjects.
To evaluate the safety and pharmacokinetics of probucol by multiple oral administration in healthy male subjects.
The purpose of the study is to compare the pharmacokinetics of fentanyl following i.v. and oral administration in healthy volunteers, and to assess the bioavailability of fentanyl followin...
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).