Track topics on Twitter Track topics that are important to you
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
The purpose of this study was to investigate the pharmacokinetics of a single oral administration of metyrapone (MP) and metabolites produced from it in male Wistar rats, and the major tissues and enz...
Ketoprofen, a potent nonsteroidal anti-inflammatory drug, is clinically administered as a racemic mixture. One of the possible metabolism routes of ketoprofen is the inversion of the R- to S-enantiome...
Voriconazole is both a substrate and a potent inhibitor of cytochrome P450 (CYP) 3A. It has a high bioavailability and non-linear pharmacokinetics. We investigated the pharmacokinetics and metabolism ...
Daily rhythms in physiology may affect the pharmacokinetics of a drug. The aim of this study was to evaluate 24-hour variation in the pharmacokinetics of the CYP3A substrate midazolam. Oral (2 mg) and...
Ginkgo leaf tablet (GLT) is an effective traditional Chinese multi-herbal formula, which is often combined with amlodipine for treating senile hypertension in clinic. The aim of this study was to stud...
The purpose of this study is: To assess the pharmacokinetic profile and safety of ranolazine PR in healthy Korean and Caucasian volunteers after oral administration of Ranolazine at the d...
To investigate the basic pharmacokinetics of BI 1482694, its metabolites M1 and M2, and [14C]-radioactivity, including mass balance, excretion pathways and metabolism following a single or...
The objective of this study is to evaluate the safety and the pharmacokinetics of ASP2151 after multiple oral dosing of ASP2151 in healthy non-elderly male and elderly male Japanese subjec...
The primary objectives of the study are: To determine the mass balance and routes of elimination of BIIB074 and its known metabolites following administration of a single oral dose of BIIB...
The purpose of this study is to investigate the effects of multiple oral doses of LEO 32731 on the pharmacokinetics of a single oral dose of the cytochrome P450 3A substrate midazolam in h...
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).
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) 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...