Model-Based Development of Anacetrapib, a Novel Cholesteryl Ester Transfer Protein Inhibitor
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چکیده
منابع مشابه
Metabolism and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in humans.
Anacetrapib is a novel cholesteryl ester transfer protein inhibitor being developed for the treatment of primary hypercholesterolemia and mixed dyslipidemia. The absorption, distribution, metabolism, and excretion of anacetrapib were investigated in an open-label study in which six healthy male subjects received a single oral dose of 150 mg and 165 microCi of [(14)C]anacetrapib. Plasma, urine, ...
متن کاملPharmacokinetics, metabolism, and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in rats and rhesus monkeys.
The pharmacokinetics and metabolism of anacetrapib (MK-0859), a novel cholesteryl ester transfer protein inhibitor, were examined in rats and rhesus monkeys. Anacetrapib exhibited a low clearance in both species and a moderate oral bioavailability of approximately 38% in rats and approximately 13% in monkeys. The area under the plasma concentration-time curve in both species increased in a less...
متن کاملHow Anacetrapib Inhibits the Activity of the Cholesteryl Ester Transfer Protein? Perspective through Atomistic Simulations
Cholesteryl ester transfer protein (CETP) mediates the reciprocal transfer of neutral lipids (cholesteryl esters, triglycerides) and phospholipids between different lipoprotein fractions in human blood plasma. A novel molecular agent known as anacetrapib has been shown to inhibit CETP activity and thereby raise high density lipoprotein (HDL)-cholesterol and decrease low density lipoprotein (LDL...
متن کاملDisposition into Adipose Tissue Determines Accumulation and Elimination Kinetics of the Cholesteryl Ester Transfer Protein Inhibitor Anacetrapib in Mice.
The cholesteryl ester transfer protein (CETP) inhibitor anacetrapib exhibits a long terminal half-life (t½) in humans; however, the dispositional mechanisms that lead to this long t½ are still being elucidated. As it is hypothesized that disposition into adipose tissue and binding to CETP might play a role, we sought to delineate the relative importance of these factors using a preclinical anim...
متن کاملPlasma cholesteryl ester transfer protein.
The plasma lipoproteins are continuously remodeled during their transit through the plasma compartment, owing to the action of lipid metabolizing enzymes and lipid transfer processes. These activities have a major effect on the composition, size, and concentration of the lipoproteins. Lipid transfer processes involving neutral lipids and phospholipids are mediated by specialized plasma proteins...
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ژورنال
عنوان ژورنال: The AAPS Journal
سال: 2011
ISSN: 1550-7416
DOI: 10.1208/s12248-011-9254-0