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New therapies targeting apoB metabolism for high-risk patients with inherited dyslipidaemias: what can the clinician expect?

, : New therapies targeting apoB metabolism for high-risk patients with inherited dyslipidaemias: what can the clinician expect?. Cardiovascular Drugs and Therapy 27(6): 559-567

Apolipoprotein B (apoB) has a key role in the assembly and secretion of very low-density lipoprotein (VLDL) from the liver. Plasma apoB concentration affects the number of circulating atherogenic particles, and serves as an independent predictor of the risk of atherosclerotic cardiovascular disease. While statins are the most potent apoB-lowering agents currently prescribed, their efficacy in achieving therapeutic targets for low-density lipoprotein cholesterol (LDL-C) in high-risk patients, such as those with familial hypercholesterolaemia (FH), is limited. Resistance and intolerance to statins also occurs in a significant number of patients, necessitating new types of lipid-lowering therapies. Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9; AMG 145 and REGN727), a sequence-specific antisense oligonucleotide against apoB mRNA (mipomersen) and a synthetic inhibitor of microsomal triglyceride transfer protein (MP; lomitapide) have been tested in phase III clinical trials, particularly in patients with FH. The trials demonstrated the efficacy of these agents in lowering apoB, LDL-C, non-high-density lipoprotein cholesterol and lipoprotein(a) by 32a 55A %, 37a 66A %, 38a 61A % and 22a 50A % (AMG 145), 21a 68A %, 29a 72A %, 16a 60A % and 8a 36A % (REGN727), 16a 71A %, 15a 71A %, 12a 66A % and 23a 49A % (mipomersen) and 24a 55A %, 25a 51A %, 27a 50A % and 15a 19A % (lomitapide), respectively. Monoclonal antibodies against PCSK9 have an excellent safety profile and may be indicated not only in heterozygous FH, but also in statin-intolerant patients and those with other inherited dyslipidemias, such as familial combined hyperlipidaemia and familial elevation in Lp(a). Mipomersen and lomitapide increase hepatic fat content and are at present indicated for treating adult patients with homozygous FH alone.


PMID: 23913122

DOI: 10.1007/s10557-013-6479-4

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Mikamo, H.; Tanaka, K.; Watanabe, K.; Tamaya, T.; Izumi, K., 2006: Clinical investigation on administration method of gatifloxacin based on PK/PD theory. There have not been sufficient clinical studies based on pharmacokinetics/pharmacodynamics (PK/PD) theory, on which many clinical doctors have recently focused. To consider the optimized administration method based on PK/PD theory for gatifloxacin...

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