In Silico Prediction and Pharmacokinetic Comparison of Ursodeoxycholic Acid and Obeticholic Acid in the Management of Primary Biliary Cholangitis

Abstract

Background: Primary Biliary Cholangitis (PBC) is a persistent liver disease. Ursodeoxycholic acid is used as a first-line treatment for the past two decades. However, concurrent use of Ursodeoxycholic acid reported with a severe adverse drug reaction. Obeticholic acid has been started utilizing as monotherapy and also with Ursodeoxycholic acid in a patient who is intolerant to Ursodeoxycholic acid therapy. We primarily aimed to compare the pharmacokinetic & toxicity profiles of Ursodeoxycholic acid and Obeticholic acid using in silico methods. Method: The pharmacokinetic profile of UDCA & OCA was observed from PKCSM server online database, OSIRIS® property Explorer, T.E.S.T. (Toxicity estimation software tool) & Molinspiration® is used to estimate the drug toxicity profiles. Result: This computer-aided response provides a great understanding and creates a gap between the theoretical and clinical evidence for UDCA & OCA's preference in PBC management. Conclusion: Co-administration of Obeticholic acid with Ursodeoxycholic acid will be an effective treatment for PBC in patients with UDCA intolerants. However, both medications are well-recognized substrates of the CYP3A4 enzyme and may lead to unintended drug interactions and side effects. Keywords: Primary Biliary Cholangitis, Obeticholic acid, Ursodeoxycholic acid, CYP3A4, Drug Interactions, Pharmacokinetics.