HMG CoA-Reductase Inhibitors

| Home | | Medicinal Chemistry |

Chapter: Medicinal Chemistry : Antihyperlipidaemic Agents

Antihyperlipidaemic Agents : HMG CoA-Reductase Inhibitors - Synthesis and Drug Profile - i. Simvastatin (Simvas, Zosta, Siravotin) ii. Fluvastatin iii. Dalvastatin iv. Lovastatin


SYNTHESIS AND DRUG PROFILE


HMG CoA-Reductase Inhibitors

Mode of action: These kinds of drugs competitively inhibit the conversion of 3-hyroxy-3-methyl glutaryl coenzyme (HMG CoA) to mevalonate, which is the rate-limiting step in cholesterol synthesis and results in receptor mediated uptake and catabolism of intermediate density lipoprotein and very low-density lipoprotein.

Synthesis of Cholesterol


Metabolism of HMG CoA-reductase inhibitors: Lovastatin and simvastain are inactive prodrugs that must undergo in vivo hydrolysis to produce their effects. The active forms of these two compounds as well as most HMGRIs undergo extensive first pass metabolism. The CYP3A4 isoenzyme is responsible for the oxidative metabolism of atrovastatin, lovastatin, and simvastatin. In the case of atrovastatin, the orthoand para-hydroxylated metabolites are equiactive with the parent compound and contribute significantly to the overall activity of drugs.


i. Simvastatin (Simvas, Zosta, Siravotin)


Properties and uses: It is a white or almost white crystalline powder, insoluble in water, well soluble in methylene chloride and in alcohol. It is used as an antihyperlipidaemic agent.

Assay: It is assayed by adopting liquid chromatography technique.

Storage: It should be stored in well-closed airtight containers under nitrogen and protected from light.

Dose: For hyperlipidaemias: Prevention of cardiovascular events: Adult: Initially, 10–20 mg/day, to be taken in the evening. May start with 40 mg once daily in patients with high cardiovascular risk. For patients with moderate cardiovascular risk, initiate with 10 mg once daily, may adjust dose at 4-weekly intervals. Maximum of 80 mg/day.

For homozygous familial hypercholesterolaemia: Adult: Intially, 40 mg once daily. May increase dose to 80 mg daily, given in three divided doses. Child: 10–17 years: Initially, 10 mg daily. May increase to 40 mg daily according to response.

Dosage forms: Simvastatin tablets B.P.


ii. Fluvastatin


Synthesis


Metabolism: It is metabolized by the CYPC9 and CYP3A4 isoenzymes to active hydroxylated metabolites, however, these metabolites do not circulate systematically and do not contribute to the overall activity.

Properties and uses: It exists as a white to pale yellow hygroscopic powder, soluble in methanol and water or ethanol. It is used as an antihyperlipidaemic agent.


iii. Dalvastatin


Synthesis



iv. Lovastatin


Properties and uses: It is a white or almost white crystalline powder, insoluble in water, soluble in acetone, and sparingly soluble in ethanol. Used as HMG Co-A reductase inhibitor and lipid-regulating drug.

Assay: It is assayed by adopting liquid chromatography technique.

Storage: It should be stored in well-closed airtight containers under nitrogen at a temperature of 2°C to 8°C.


Contact Us, Privacy Policy, Terms and Compliant, DMCA Policy and Compliant

TH 2019 - 2022 pharmacy180.com; Developed by Therithal info.