APO-LOVASTATIN TABLET 40mg FOR ORAL USE

Product Information

Registration Status: Active

APO-LOVASTATIN TABLET 40mg is approved to be sold in Singapore with effective from 1998-03-03. It is marketed by PHARMAFORTE SINGAPORE PTE LTD, with the registration number of SIN09663P.

This product contains Lovastatin 40mg in the form of TABLET. It is approved for ORAL use.

This product is manufactured by APOTEX INC in CANADA.

It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Description

Lovastatin is a cholesterol-lowering agent that belongs to the class of medications called statins. It was the second agent of this class discovered. It was discovered by Alfred Alberts and his team at Merck in 1978 after screening only 18 compounds over 2 weeks. The agent, also known as mevinolin, was isolated from the fungi Aspergillus terreus. Research on this compound was suddenly shut down in 1980 and the drug was not approved until 1987. Interesting, Akira Endo at Sankyo Co. (Japan) patented lovastatin isolated from Monascus ruber four months before Merck. Lovastatin was found to be 2 times more potent than its predecessor, mevastatin, the first discovered statin. Like mevastatin, lovastatin is structurally similar to hydroxymethylglutarate (HMG), a substituent of HMG-Coenzyme A (HMG-CoA), a substrate of the cholesterol biosynthesis pathway via the mevalonic acid pathway. Lovastatin is a competitive inhibitor of HMG-CoA reductase with a binding affinity 20,000 times greater than HMG-CoA. Lovastatin differs structurally from mevastatin by a single methyl group at the 6’ position. Lovastatin is a prodrug that is activated by in vivo hydrolysis of the lactone ring. It, along with mevastatin, has served as one of the lead compounds for the development of the synthetic compounds used today.

Indication

For management as an adjunct to diet to reduce elevated total-C, LDL-C, apo B, and TG levels in patients with primary hypercholesterolemia and mixed dyslipidemia. For primary prevention of coronary heart disease and to slow progression of coronary atherosclerosis in patients with coronary heart disease.

Mechanism of Action

Lovastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Lovastatin is a prodrug that is activated in vivo via hydrolysis of the lactone ring to form the β-hydroxyacid. The hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind to HMG-CoA reductase with 20,000 times greater affinity than its natural substrate. The bicyclic portion of lovastatin binds to the coenzyme A portion of the active site.

Pharmacokinetics

Absorption: Studies suggest that <5% of the oral dose reaches the general circulation as active inhibitors. Time to peak serum concentration is 2-4 hours. Lovastatin undergoes extensive first-pass metabolism so the availability of the drug in the system is low and variable.
Distribution: Lovastatin is able to cross the blood-brain-barrier and placenta.
Metabolism: Lovastatin is hepatically metabolized in which the major active metabolites are the β-hydroxyacid of lovastatin, the 6’-hydroxy derivative, and two additional metabolites.
Elimination

Toxicity

LD₅₀>1000 mg/kg (orally in mice)

Active Ingredient/Synonyms

Source of information: Drugbank (External Link). Last updated on: 3^rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.