Fig. 1.

Mechanism of action and physiologic sites of bempedoic acid metabolism, activation, biologic activity, and clearance. Following oral administration, bempedoic acid is converted to its active metabolite bempedoyl-CoA by ASCVL1 in the liver. Bempedoyl-CoA inhibits the cytoplasmic ACL enzyme, which converts citrate to acetyl-CoA in the cholesterol synthesis pathway, leading to upregulation of LDLR. ASCVL1 is not present in the muscle so is not converted to bempedoyl-CoA. Clearance of bempedoic acid and bempedoyl-CoA is primarily enacted by glucuronidation and subsequent renal elimination. Bempedoic acid is a weak inhibitor of OAT2, resulting in minor increases in plasma uric acid and creatinine. ACL ATP-citrate lyase, ASCVL1 very long-chain acyl-CoA syntheasae-1, HMGR 3-hydroxy-3-methylglutarate-CoA reductase, LDL-C low-density lipoprotein cholesterol, LDLR low-density lipoprotein receptor, OAT2 organic anion transporter-2