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
This study was to compare pharmacokinetics and bile transformation of R-enantiomer bambuterol with its racemate. Pharmacokinetics of R-enantiomer was investigated after single-dose intravenous and thr...
Verticinone, the main active component in F. hupehensis, exhibits potent antitussive and expectorant effects. Here, a LC-MS method was developed and applied to study the pharmacokinetics, tissue distr...
The current study aimed at the evaluation of, in vivo, the effect of omeprazole on the pharmacokinetics of rosuvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. Omeprazo...
Hypaconitine (HC) is one of the main aconitum alkaloids in Aconitum carmichaelii (AC), which is considered to be effective on cardiovascular disease, although it also has high toxicity. Sini Decoction...
The study was aimed at investigating the pharmacokinetics of amoxicillin trihydrate (AMOX) in olive flounder (Paralichthys olivaceus) following oral, intramuscular, and intravenous administration, usi...
To establish the maximum tolerated dose (MTD) of oral afatinib (BIBW2992) given in combination with gemcitabine or docetaxel in patients with relapsed or refractory tumors. To assess the ...
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.
This is a multinational, double-blind, randomized, parallel-group Phase 2 clinical trial evaluating the efficacy of Afatinib (CT) .and Afatinib (GIOTRIF).
The aim of the study is to determine the Maximum Tolerated Dose (MTD) of afatinib in combination with 3-weekly trastuzumab in HER2 overexpressing cancer and to assess the efficacy of afati...
The purpose of the study is to characterize the absorption, distribution, metabolism and excretion (ADME) of a single oral dose of [14C]AZD1981
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).