Article: Lovastatin

Lovastatin
Systematic (IUPAC) name
[8-[2-(4-hydroxy-6-oxo-oxan-2-yl)ethyl] -3,7-dimethyl-1,2,3,7,8,8a- hexahydronaphthalen- 1-yl] 2-methylbutanoate
Identifiers
CAS number	75330-75-5
ATC code	C10AA02
PubChem	53232
DrugBank	APRD00370
Chemical data
Formula	C24H36O5
Mol. weight	404.54 g/mol
Pharmacokinetic data
Bioavailability	?
Protein binding	>95%
Metabolism	?
Half life	5.3 hours
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	oral

Lovastatin is a member of the drug class of statins, used for lowering cholesterol (hypolipidemic agent) in those with hypercholesterolemia and so preventing cardiovascular disease.

History

Lovastatin was isolated from a strain of Aspergillus terreus and it was the first statin approved by the FDA (August 1987).

Lovastatin is also naturally produced by certain higher fungi such as Pleurotus ostreatus (oyster mushroom) and closely related Pleurotus spp.^[1]

In 1998, the US Food and Drug Administration (FDA) placed a ban on the sale of dietary supplements derived from red yeast rice, which naturally contains lovastatin, arguing that products containing prescription agents require drug approval.

Pharmacology and dose

Main article: statin

The mode of action of statins is HMG-CoA reductase enzyme inhibition. This enzyme is needed by the body to make cholesterol.

Lovastatin causes cholesterol to be lost from LDL, but also reduces the concentration of circulating LDL (low density lipoprotien) particles. Apolipoprotein B concentration falls substantially during treatment with lovastatin. Lovastatin's ability to lower LDL is thought to be due to a reduction in VLDL, which is a precursor to LDL. Also, Lovastatin may increase the number of LDL receptors on the surface of cell membranes, and thus increase the breakdown of LDL.

Lovastatin can also produce slight to moderate increases in HDL, and slight to moderate decreases in triglycerides. Both of these effects are benefical typically beneficial to a patient with a poor lipid profile.

Both lovastatin and its b-hydroxyacid metabolite are highly bound (>95%) to human plasma proteins. Animal studies demonstrated that lovastatin crosses the blood-brain and placental barriers.^[2] Elderly patients, or those with renal insufficiency may have higher plasma concentrations of lovastatin after administration and may require a lower dose. The usual recommended starting dose is 20 mg once a day given with the evening meal, and the dose range is 10-80 mg a day in a single dose, or divided into two doses.

Side effects

Lovastatin is usually well tolerated. Lovastatin, and all statin drugs, can rarely cause myopathy or rhabdomyolysis. This can be life threatening if not recognised and treated in time and so any unexplained muscle pain or weakness whilst on lovastain should be promptly mentioned to the prescribing doctor.

Drug interactions

As with all the statin drugs, drinking grapefruit juice during therapy increases the risk of serious side effects. Grapefruit juice inhibits CYP3A4, and thus decreases the metabolism of statins, increasing their plasma concentrations.

Lovastatin at doses higher than 20 mg per day should not be used in conjunction with gemfibrozil, niacin, cyclosporin, or other fibrates. This is because of the significantly increased risk of rhabdomyolysis.

Brand names

• Mevacor®
• Advicor® (as a combination with niacin)
• Altocor®
• Altoprev®

Footnotes

1. ^ Bobek P, Ozdín L, Galbavý S (1998). "Dose- and time-dependent hypocholesterolemic effect of oyster mushroom (Pleurotus ostreatus) in rats.". Nutrition 14 (3): 282-6. PMID 9583372.
2. ^ Lovastatin. Rxlist.com.