Acipimox

Acipimox (trade name Olbetam in Europe) is a niacin derivative used as a lipid-lowering agent. It reduces triglyceride levels and increases HDL cholesterol. It may have less marked adverse effects than niacin, although it is unclear whether the recommended dose is as effective as standard doses of niacin.

Acipimox

Clinical data
Trade names	Olbetam
AHFS/Drugs.com	UK Drug Information
Routes of administration	Oral
ATC code	C10AD06 (WHO)
Legal status
Legal status	UK: POM (Prescription only)
Pharmacokinetic data
Bioavailability	100%
Protein binding	None
Metabolism	None
Elimination half-life	Phase 1: 2 hrs Phase 2: 12–14 hrs
Excretion	Renal
Identifiers
IUPAC name 5-Carboxy-2-methyl-1-oxidopyrazin-1-ium
CAS Number	51037-30-0 Y
PubChem CID	5310993
IUPHAR/BPS	1596
ChemSpider	4470534 Y
UNII	K9AY9IR2SD
KEGG	D07190 Y
ChEMBL	ChEMBL345714 Y
CompTox Dashboard (EPA)	DTXSID2046202
ECHA InfoCard	100.051.736
Chemical and physical data
Formula	C6H6N2O3
Molar mass	154.125 g·mol−1
3D model (JSmol)	Interactive image
SMILES [O-][n+]1c(cnc(C(=O)O)c1)C
InChI InChI=1S/C6H6N2O3/c1-4-2-7-5(6(9)10)3-8(4)11/h2-3H,1H3,(H,9,10) Y Key:DJQOOSBJCLSSEY-UHFFFAOYSA-N Y
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Contraindications

Contraindications are peptic ulcers, acute bleeding, recent heart attack, acute decompensated heart failure, and severe chronic kidney disease.^[1]

Adverse effects

As with niacin and related drugs, the most common adverse effects are flushing (associated with prostaglandin D₂^[2]) and gastrointestinal disturbances such as indigestion, which occur in at least 10% of patients.^[1] Flushing can be reduced by taking aspirin 20 to 30 minutes before taking acipimox. Palpitations have also been described.^{[citation needed]} High doses can cause headache,^[3] and precipitate gout.^{[citation needed]} In contrast to niacin, no impairment of glucose tolerance and no disorders of liver function have been found in studies, even under high doses of acipimox.^[1][3]

Interactions

No interactions with other drugs are known. Theoretically, combination with statins and fibrates could increase the incidence of myalgia. Alcohol can increase the risk of flushing.^[1][3]

Pharmacology

Mechanism of action

Like niacin, acipimox acts on the niacin receptor 1, inhibiting the enzyme triglyceride lipase. This reduces the concentration of fatty acids in the blood plasma and their inflow into the liver. Consequently, VLDL cholesterol production in the liver is reduced, which leads indirectly to a reduction in LDL and increase in HDL cholesterol.^[1][2]

Pharmacokinetics

Acipimox is completely absorbed from the gut. It is not bound to blood plasma proteins and not metabolized. Elimination occurs in two phases, the first having a half-life of two hours, the second of 12 to 14 hours. The substance is eliminated via the kidney.^[1]

References

1. Haberfeld H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag.
2. Benyó Z, Gille A, Kero J, Csiky M, Suchánková MC, Nüsing RM, et al. (December 2005). "GPR109A (PUMA-G/HM74A) mediates nicotinic acid-induced flushing". The Journal of Clinical Investigation. 115 (12): 3634–40. doi:10.1172/JCI23626. PMC 1297235. PMID 16322797.
3. Dinnendahl V, Fricke U, eds. (1989). Arzneistoff-Profile (in German). Vol. 1 (6 ed.). Eschborn, Germany: Govi Pharmazeutischer Verlag. ISBN 978-3-7741-9846-3.