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

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

HCIP: An Online database for prediction CYP450 Enzyme Inhibition potential of bioactive compounds

Background: Concomitant administration of herbal medicine and conventional may lead to severe metabolism-oriented herb-drug interactions. However, detecting herb-drug interaction is expensive and higher time-consuming. Several computer-aided techniques have been proposed in recent years to predict drug interactions. However, most of the methods cannot predict herb-drug interactions effectively. Methods: Canonical SMILES of bioactive compounds was gathered from the PubChem online database, and its inhibition details were gathered PKCSM from the webserver. Results: By searching the bioactive compound name in the search bar of “The Herb-CYP450 Enzyme Inhibition Predictor online database” (HCIP- http://hcip.in/), it will provide the liver enzyme inhibition profile of the selected bioactive compound. For example; Guggulsterone:  CYP3A4 inhibitor.  Conclusion: The Herb-CYP450 Enzyme Inhibition Predictor online database is very peculiar and easy to determine the inhibition profile of the targeted bioactive compound. Keywords: CYP450; Enzyme inhibition; Bioactive Compounds; Online database; Herb-Drug Interactio