Effects of NK-104, a new hydroxymethylglutaryl-coenzyme reductase inhibitor, on low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia

Kajinami, Kouji; Koizumi, Junji; Ueda, Kosei; Miyamoto, Susumu; Takegoshi, Tadayoshi; Mabuchi, Hiroshi

doi:10.1016/s0002-9149(99)00656-6

Cited by 70 publications

(50 citation statements)

References 16 publications

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“…shown a favorable safety and tolerability profile of pitavastatin in a broad range of patients. [9][10][11][12] The limitations of this study should be and source are credited.…”

Section: Secondary Efficacy Variablesmentioning

confidence: 99%

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Long-term efficacy of pitavastatin versus simvastatin

Eriksson

Budinski²,

Hounslow³

2011

Adv Therapy

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“…shown a favorable safety and tolerability profile of pitavastatin in a broad range of patients. [9][10][11][12] The limitations of this study should be and source are credited.…”

Section: Secondary Efficacy Variablesmentioning

confidence: 99%

“…10,11 Pitavastatin has also been shown to produce sustained increases in HDL-C concentrations over 52 weeks. 12 Unlike other statins, pitavastatin does not undergo extensive metabolism by cytochrome P450 isoenzymes, and hence the potential for interactions with drugs that are metabolized by cytochrome P450 is low.…”

Section: Introductionmentioning

confidence: 99%

Long-term efficacy of pitavastatin versus simvastatin

Eriksson

Budinski²,

Hounslow³

2011

Adv Therapy

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“…Pitavastatin (NK-104) is a novel synthetic potent and selective inhibitor of HMGCoA reductase, the rate-limiting enzyme in cholesterol biosynthesis (Aoki et al, 1997). This compound is known to lower plasma total cholesterol levels and reduce triglyceride levels (Kajinami et al, 2000). We recently reported that pitavastatin can protect against the hippocampal CA1 neuronal damage after transient cerebral ischemia in gerbils (Kumagai et al, 2004;Muramatsu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Alterations of Interneurons of the Gerbil Hippocampus after Transient Cerebral Ischemia: Effect of Pitavastatin

Himeda

Hayakawa

Tounai

et al. 2005

Neuropsychopharmacol

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We investigated the immunohistochemical alterations of parvalbumin (PV)-expressing interneurons in the hippocampus after transient cerebral ischemia in gerbils in comparison with neuronal nitric oxide synthase (nNOS)-expressing interneurons. We also examined the effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor pitavastatin against the damage of neurons and interneurons in the hippocampus after cerebral ischemia. Severe neuronal damage was observed in the hippocampal CA1 pyramidal neurons 5 and 14 days after ischemia. The PV immunoreactivity was unchanged up to 2 days after ischemia. At 5 and 14 days after ischemia, in contrast, a conspicuous reduction of PV immunoreactivity was observed in interneurons of the hippocampal CA1 sector. Furthermore, a significant decrease of PV immunoreactivity was found in interneurons of the hippocampal CA3 sector. No damage of nNOS-immunopositive interneurons was detected in the gerbil hippocampus up to 1 day after ischemia. Thereafter, a decrease of nNOS immunoreactive interneurons was found in the hippocampal CA1 sector up to 14 days after ischemia. Pitavastatin significantly prevented the neuronal cell loss in the hippocampal CA1 sector 5 days after ischemia. Our immunohistochemical study also showed that pitavastatin prevented significant decrease of PV-and nNOS-positive interneurons in the hippocampus after ischemia. Double-labeled immunostainings showed that PV immunoreactivity was not found in nNOS-immunopositive interneurons of the brain. The present study demonstrates that cerebral ischemia can cause a loss of both PV-and nNOS-immunoreactive interneurons in the hippocampal CA1 sector. Our findings also show that the damage to nNOS-immunopositive interneurons may precede the neuronal cell loss in the hippocampal CA1 sector after ischemia and nNOS-positive interneurons may play some role in the pathogenesis of cerebral ischemic diseases. Furthermore, our present study indicates that pitavastatin can prevent the damage of interneurons in the hippocampus after cerebral ischemia. Thus, our study provides valuable information for the pathogenesis after cerebral ischemia.

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“…Results indicate that doses of 2 mg to 4 mg significantly reduced LDL cholesterol levels by 40 to 48% from baseline. 33,34 In a 12-week doubleblind dose-finding study, pitavastatin 1 mg to 4 mg produced significant LDL cholesterol reductions of 34 to 47% in 273 patients with hyperlipidemia. 35 A comparative study of the same duration in 240 subjects with primary hypercholesterolemia found that pitavastatin 2 mg decreased LDL cholesterol levels by 38%, which was significantly greater than the reduction with pravastatin, the comparator drug.…”

Section: Statins In Developmentmentioning

confidence: 99%

Treating hypercholesterolemia: Looking forward

Gotto

2003

Clin Cardiol

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Summary: Despite important advances in the management of hypercholesterolemia in recent decades, many patients with lipid disorders remain unidentified or undertreated and so continue to have unfavorable levels of low-density lipoprotein (LDL) cholesterol and an increased risk for coronary events. The statins-which inhibit 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in cholesterol biosynthesis-have proved to be the most powerful pharmacologic agents for lowering serum lipids, and newer statins offer even greater efficacy than the agents introduced 10 to 15 years ago. Studies have shown that rosuvastatin, in late-stage development, is a very potent agent for the treatment of primary hypercholesterolemia, and that relatively low doses decrease LDL cholesterol levels to a greater extent than do similar doses of pravastatin, simvastatin, or atorvastatin as evaluated in separate clinical trials. Pitavastatin, in phase II trials, also has promise as a more potent drug than currently available statins. Because neither of these drugs has been approved for use in the United States, clinical trial results should be considered preliminary. In the future, agents that combine the actions of statins and nicotinic acid may achieve still greater LDL cholesterol reductions. Drugs that lower lipids via mechanisms other than inhibition of HMG-CoA reductase also offer promise. The newest addition to the roster of lipidregulating agents is ezetimibe, a cholesterol absorption inhibitor that has been approved for use either alone or in combination with a statin. Agents in development include bile acid transport inhibitors and inhibitors of acyl CoA:cholesterol acyltransferase. More research will be needed to determine the full clinical potential of such approaches to the management of hypercholesterolemia.

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Effects of NK-104, a new hydroxymethylglutaryl-coenzyme reductase inhibitor, on low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia

Cited by 70 publications

References 16 publications

Long-term efficacy of pitavastatin versus simvastatin

Long-term efficacy of pitavastatin versus simvastatin

Alterations of Interneurons of the Gerbil Hippocampus after Transient Cerebral Ischemia: Effect of Pitavastatin

Treating hypercholesterolemia: Looking forward

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