Lomitapide Mesylate is a MTTP inhibitor with IC50 of 8 nM, used as a complement to a low-fat diet and other lipid-lowering treatments in patients with homozygous familial hypercholesterolemia.
Microsomal triglyceride transfer protein (MTP) is a multifunctional protein, and its deregulation during pathophysiological conditions gives rise to different metabolic conditions[3]. MTP plays an essential role in lipid metabolism, especially in the biogenesis of very low-density lipoproteins and chylomicrons via the transfer of neutral lipids and the assembly of apoB-containing lipoproteins[4]. Lomitapide is a small-molecule, MTP inhibitor, for the treatment of both familial and primary hypercholesterolemia. Oral, once-daily lomitapide will be targeted at patients resistant to HMG-CoA reductase inhibitors (statins) either due to abnormalities in liver function or to discontinuation because of muscle pain[5]. Lomitapide is an orally administered inhibitor of the microsomal triglyceride transfer protein, inhibits the synthesis of chylomicrons and very low-density lipoprotein, thereby reducing plasma levels of low-density lipoprotein cholesterol (LDL-C)[6]. Lomitapide undergoes hepatic metabolism via cytochrome P-450 (CYP) isoenzyme 3A4 and interacts with CYP3A4 substrates including atorvastatin and simvastatin; dose adjustment is recommended when lomitapide is used concurrently with these agents[7]. In the presence of an up-titration regiment and low-fat diet, lomitapide is generally well tolerated and liver fat accumulation stabilizes after the initial increase. Elevation of alanine aminotranferase levels greater than 3 times the upper limit of normal can be managed successfully with temporary dose reduction[8].
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