Chenodeoxycholic Acid (DB06777): A Comprehensive Pharmacological and Clinical Monograph

Executive Summary

Chenodeoxycholic acid (CDCA) is an endogenous primary bile acid synthesized in the liver from cholesterol, playing a fundamental role in lipid digestion and metabolic homeostasis. Beyond its physiological function, CDCA has been developed as a therapeutic agent, identified by DrugBank ID DB06777, with a unique and evolving clinical profile. This monograph provides a comprehensive analysis of its chemistry, pharmacology, clinical applications, safety, and regulatory status.

Initially approved for the dissolution of radiolucent cholesterol gallstones in patients with high surgical risk, CDCA's use in this indication has diminished due to modest efficacy rates, a high incidence of adverse effects, and the advent of superior therapeutic alternatives. However, a deeper understanding of its mechanism of action has led to a clinical renaissance for the drug. CDCA is now established as the first-line, life-altering replacement therapy for Cerebrotendinous Xanthomatosis (CTX), a rare, autosomal recessive lipid storage disease. In CTX, CDCA corrects the core biochemical defect, preventing irreversible neurological damage and other systemic complications.

The pharmacological actions of CDCA are primarily mediated through its potent agonist activity at the Farnesoid X Receptor (FXR), a nuclear receptor that governs the expression of genes involved in bile acid, cholesterol, and glucose metabolism. This mechanism underpins both its ability to desaturate biliary cholesterol for gallstone dissolution and its capacity to restore metabolic balance in CTX.