Obeticholic acid, sold under the brand name Ocaliva, is a semi-synthetic bile acid analogue which has the chemical structure 6α-ethyl-chenodeoxycholic acid. It is used as a medication used to treat primary biliary cholangitis. Chemically it is derived from chenodeoxycholic acid with an ethyl substituent at the 6α position, approximate molecular formula C26H44O4 and molecular weight near 424.6 g/mol. It is a high-affinity farnesoid X receptor agonist that modulates bile acid synthesis and transport, reducing CYP7A1-mediated bile acid production and upregulating bile salt export proteins; pharmacologically this leads to reduced intrahepatic bile acid accumulation and downstream anti-inflammatory and anti-fibrotic signaling in cholestatic disease. Obeticholic acid is administered orally as film-coated tablets commonly dosed at 5 mg or 10 mg; it undergoes extensive hepatic conjugation to glycine and taurine conjugates, shows low to moderate systemic free drug exposure, is eliminated predominantly via the biliary-fecal route, and is analyzed and controlled in production by validated HPLC and LC-MS methods for potency and related substances.
Parent: Obeticholic
Production and quality control of obeticholic acid routinely monitor related compounds and degradation products including epimeric isomers, dehydrogenated derivatives, 7-keto and 3-oxo oxidation products, positional isomers and residual synthetic intermediates; common metabolite conjugates such as the glycine and taurine conjugates are characterized separately. Typical specification ranges used in pharmaceutical quality control are individual identified related compounds controlled at not more than 0.2 to 0.5 percent w/w, unspecified single impurities limited to not more than 0.1 to 0.5 percent w/w depending on identification and qualification status, and total impurities generally limited to not more than 1.0 percent w/w; genotoxic impurity thresholds follow ICH M7 guidance and are controlled to relevant microgram per day limits. Routine analytical approaches for impurity profiling include gradient HPLC with UV detection, LC-MS for mass confirmation, and forced-degradation studies to define degradation pathways and validate stability-indicating methods.
Obeticholic acid is approved for the treatment of primary biliary cholangitis to improve liver biochemistry in patients with an inadequate response to ursodeoxycholic acid or as monotherapy when ursodeoxycholic acid is not tolerated; it works by activating the farnesoid X receptor to reduce bile acid synthesis and improve bile flow.
Obeticholic acid has been investigated in nonalcoholic steatohepatitis clinical trials and demonstrated some histologic improvements in fibrosis and steatohepatitis endpoints, but it is not broadly approved for fatty liver disease in many regions, and potential benefits must be balanced against adverse effects such as pruritus and changes in lipid profile; clinical use for fatty liver should follow current guideline recommendations and specialist assessment.
Obeticholic acid is a potent agonist of the farnesoid X receptor, a nuclear transcription factor that suppresses bile acid synthesis by downregulating CYP7A1, increases expression of bile salt export proteins and transporters, and modulates inflammatory and fibrotic signaling pathways in the liver.
Cost varies substantially by country, dosage strength, payer coverage and pharmacy; retail prices in some markets can amount to several thousand US dollars per month without insurance, while patient assistance programs, insurance formularies and negotiated discounts commonly reduce out-of-pocket expense, so contact local pharmacies or payers for an accurate, current price.
