Bempedoic acid

Bempedoic acid is a Antilipemic Agents belongoing to Adenosine triphosphate-citrate lyase (ACL) inhibitors

Bempedoic acid is used as an adjunct to diet and maximally tolerated statin therapy for the

treatment of adults with heterozygous familial hypercholesterolemia or established

atherosclerotic cardiovascular disease who require additional lowering of LDL-C.

Bempedoic acid is rapidly absorbed in the small intestine.The apparent volume of distribution of bempedoic acid is about 18L.The plasma protein binding of bempedoic acid and its metabolites is about 99%.The two main metabolites of bempedoic metabolism are ETC-1002-CoA3 and ESP15228. Bempedoic acid is primarily eliminated via the metabolism of its acyl glucuronide. This drug is reversibly converted to an active metabolite based on observations during in vitro studies. Both compounds resulting from the metabolism of bempedoic acid are metabolized to become inactive glucuronide conjugates by the enzyme UGT2B7.

Bempedoic acid’s conjugates are primarily eliminated via the urine (70%) and the feces (30%). A total of 5% of the Unchanged drug is excreted in the urine and feces, combined

The Tmax of Bempedoic acid was found to be about approximately 3.5 hours.

Bempedoic acid shows common side effects like weight loss, headache, abdominal pain, nausea

Bempedoic acid is available in Tablet

Bempedoic acid is available in India, Germany, Canada, France, USA.

Bempedoic acid inhibits the synthesis of cholesterol in the liver, reducing LDL-C levels. This reduces the development of atherosclerotic plaques that may increase the risk of cardiovascular events. Earlier clinical trials studying the effects of bempedoic acid showed a dose‐dependent reduction of LDL‐C levels in addition to decreased LDL particle number, and reduced levels of apolipoprotein B, non–HDL cholesterol, and high‐sensitivity C‐reactive protein.

Bempedoic acid is available in the form of tablets.

Bempedoic acid is used as an adjunct to diet and maximally tolerated statin therapy for the treatment of adults with heterozygous familial hypercholesterolemia or established

atherosclerotic cardiovascular disease who require additional lowering of LDL-C.

Bempedoic acidis a prodrug that requires activation in the liver. The very-long-chain acyl-CoA synthetase-1 (ACSVL1) enzyme is responsible for its activation to ETC-1002-CoA, the pharmacologically active metabolite. ATP lyase (also known as ATP synthase) plays an important part of cholesterol synthesis. BETC-1002-CoA directly inhibits this enzyme after the parent drug is activated in the liver by coenzyme A (CoA).

Bempedoic acid is approved for use in the following clinical indications

Bempedoic acid is indicated as an adjunct to diet and maximally tolerated statin therapy for the Treatment of adults with heterozygous familial hypercholesterolemia or established.

Atherosclerotic cardiovascular disease who require additional lowering of LDL-C.

Bempedoic acid is available in the dosage strength of 180 mg.

Bempedoic acid is available in the form of Tablets.

Take after eating and with a full glass of water to decrease gastric upset.

Hyperuricemia

Bempedoic acid inhibits renal tubular OAT2 and may increase blood uric acid levels. In clinical trials, 26% of Bempedoic acid -treated patients with normal Baseline uric acid values (versus 9.5% placebo) experienced hyperuricemia one or more times, and 3.5% of patients experienced clinically significant hyperuricemia reported as an adverse Reaction (versus 1.1% placebo). Increases in uric acid levels usually occurred within the first 4 weeks of treatment initiation and persisted throughout treatment. After 12 weeks of treatment, the mean placebo-adjusted increase in uric acid compared to baseline was 0.8 mg/dL for patients Treated with Bempedoic acid. Elevated blood uric acid may lead to the development of gout. Gout was reported in 1.5% of Patients treated with Bempedoic acid and 0.4% of patients treated with placebo. The risk for gout Placebo), although gout also occurred more frequently than placebo in patients treated with Bempedoic acid who had no prior gout history (1.0% Bempedoic acid versus 0.3% placebo). Advise patients to contact their healthcare provider if symptoms of hyperuricemia occur. Assess Serum uric acid when clinically indicated. Monitor patients for signs and symptoms of Hyperuricemia, and initiate treatment with urate-lowering drugs as appropriate.

• Tendon Rupture

Bempedoic acid is associated with an increased risk of tendon rupture or injury. In clinical trials,

Tendon rupture occurred in 0.5% of patients treated with Bempedoic acid versus 0% of placebo

Treated patients and involved the rotator cuff (the shoulder), biceps tendon, or Achilles tendon.

Tendon rupture occurred within weeks to months of starting Bempedoic acid. Tendon rupture may occur more frequently in patients over 60 years of age, in those taking corticosteroid or Fluoroquinolone drugs, in patients with renal failure, and in patients with previous tendon Disorders. Discontinue Bempedoic acid immediately if the patient experiences rupture of a tendon. Consider Discontinuing Bempedoic acid if the patient experiences joint pain, swelling, or inflammation. Advise patients to rest at the first sign of tendinitis or tendon rupture and to contact their Healthcare provider if tendinitis or tendon rupture symptoms occur. Consider alternative therapy in patients with a history of tendon disorders or tendon rupture.

Bempedoic acid is used off label to enhance leflunomide elimination. Use of the enhanced elimination procedure is recommended in all females of reproductive potential upon discontinuation of leflunomide. Pregnancy should be avoided until undetectable serum concentrations (<0.02 mg/L) of leflunomide are verified.

Common Adverse effects:

• Headache

▪ Flushing

▪ Indigestion

Less Common Adverse effects:

▪ Serious allergic reaction which causes difficulty in breathing or dizziness

▪ Difficulty in breathing or wheezing

▪ Nausea (feeling sick)

▪ Rash, itching, redness

▪ Inflammation of muscle tissue causing pain in the muscles and joints

▪ Feeling hot, malaise (generally not feeling well)

Rare Adverse effects

▪ Eye problems including dry or gritty eye

▪ Vasodilatation (widening of the blood vessels)

▪ Diarrhea

May enhance the myopathic (rhabdomyolysis) effect of statins and fibrates.

The common side effects of Bempedoic acid include the following :

• Headache
• Flushing
• Indigestion

Pharmacodynamic

• Bempedoic acid is an adenosine triphosphate-citrate lyase (ACL) inhibitor that lowers Low-density lipoprotein cholesterol (LDL-C) by inhibition of cholesterol synthesis in the liver. ACL is an enzyme upstream of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) Reductase in the cholesterol biosynthesis pathway. Bempedoic acid and its active metabolite, ESP15228, require coenzyme A (CoA) activation by very long-chain acyl-CoA synthetase (ACSVL1) to ETC-1002-CoA and ESP15228-CoA, respectively. ACSVL1 is expressed Primarily in the liver. Inhibition of ACL by ETC-1002-CoA results in decreased cholesterol Synthesis in the liver and lowers LDL-C in blood via upregulation of low-density lipoprotein Receptors.

Pharmacokinetics

● Absorption

Bempedoic acid is rapidly absorbed in the small intestine.1,2 The Tmax of the 180mg tablet is estimated at 3.5 hours.

● Distribution

The apparent volume of distribution of Bempedoic acid is about 18L.The plasma protein binding of Bempedoic acid and its metabolites is about 99%.6

● Metabolism

The two main metabolites of bempedoic metabolism are ETC-1002-CoA3 and ESP15228. Bempedoic acid is primarily eliminated via the metabolism of its acyl glucuronide. This drug is reversibly converted to an active metabolite based on observations during in vitro studies. Both compounds resulting from the metabolism of Bempedoic acid are metabolized to become inactive glucuronide conjugates by the enzyme UGT2B7.

● Route of elimination

Bempedoic acid’s conjugates are primarily eliminated via the urine (70%) and the feces (30%). A total of 5% of the Unchanged drug is excreted in the urine and feces, combined

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
• https://reference.medscape.com/drug/colestid-Bempedoic acid -342452
• https://go.drugbank.com/drugs/DB00375
• https://www.sciencedirect.com/topics/medicine-and-dentistry/Bempedoic acid
• https://europepmc.org/article/med/6988203