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

2021 ◽  
Vol 11 (2-S) ◽  
pp. 113-117
Author(s):  
Manali Sudhir Dhage ◽  
Nila Ganamurali ◽  
Dhivya Dhanasekaran ◽  
Sarvesh Sabarathinam
Keyword(s):  
Drug Interactions ◽  
Ursodeoxycholic Acid ◽  
In Silico ◽  
Software Tool ◽  
Pharmacokinetic Profile ◽  
Primary Biliary Cholangitis ◽  
Obeticholic Acid ◽  
Acid Therapy ◽  
Concurrent Use ◽  
Cyp3a4 Enzyme

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.

scholarly journals Obeticholic acid—a new therapy in PBC and NASH

2020 ◽  
Vol 133 (1) ◽  
pp. 95-104 ◽  
Author(s):  
Roger W Chapman ◽  
Kate D Lynch
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Ursodeoxycholic Acid ◽  
Farnesoid X Receptor ◽  
Primary Biliary Cholangitis ◽  
Second Line ◽  
Obeticholic Acid ◽  
Second Line Therapy ◽  
Line Therapy

Abstract Introduction Obeticholic acid (OCA) is a semi-synthetic hydrophobic bile acid (BA) analogue that is highly selective agonist of farnesoid X receptor (FXR), a key nuclear BA receptor, which induces expression of gut-derived hormones, in particular fibroblast growth factor 19. The resulting beneficial effects of OCA on glucose and lipid metabolism and particularly hepatic inflammation make it a candidate for the treatment of a variety of conditions including primary biliary cholangitis (PBC) and nonalcoholic steatohepatitis (NASH). Sources of data In PBC patients who have not initially responded to ursodeoxycholic acid, OCA has been shown in double-blind controlled clinical trials to significantly reduce serum alkaline phosphatase. To date, OCA is the only therapy licensed by the FDA, EMA and endorsed by NICE as second line therapy for PBC. No medications are currently approved in Europe or the USA for the treatment of NASH. In recent clinical trials, OCA has been shown encouraging results by improving liver blood tests and reducing liver fibrosis with no worsening of NASH. Areas of agreement OCA is the established second line therapy for PBC in those patients who fail to adequately respond to ursodeoxycholic acid. Areas of controversy The main side effects of OCA treatment in both PBC and NASH is that of dose-dependent pruritis which can lead to treatment discontinuation in ~1–10% of patients. In addition, OCA-treated patients may also exhibit (reversible) alterations in serum lipid levels; most notably a small decrease in high density lipoprotein cholesterol. It is not yet known whether these changes carry a long-term cardiovascular risk in NASH. In addition, the relatively high cost of OCA may limit its use in cash-limited health systems. Growing Points Additional clinical trials are in progress to ascertain the long-term effects of OCA on survival in PBC and NASH. Areas timely for developing research New FXR agonists with a lower rate of side effects are being developed and trialed. Combination therapy with other agents may offer increased efficacy.

scholarly journals Long-Term Obeticholic Acid Therapy Improves Histological Endpoints in Patients With Primary Biliary Cholangitis

2020 ◽  
Vol 18 (5) ◽  
pp. 1170-1178.e6 ◽  
Author(s):  
Christopher L. Bowlus ◽  
Paul J. Pockros ◽  
Andreas E. Kremer ◽  
Albert Parés ◽  
Lisa M. Forman ◽  
...  
Keyword(s):  
Primary Biliary Cholangitis ◽  
Obeticholic Acid ◽  
Acid Therapy

scholarly journals Ursodeoxycholic acid therapy and liver transplant-free survival in patients with primary biliary cholangitis

2019 ◽  
Vol 71 (2) ◽  
pp. 357-365 ◽  
Author(s):  
Maren H. Harms ◽  
Henk R. van Buuren ◽  
Christophe Corpechot ◽  
Douglas Thorburn ◽  
Harry L.A. Janssen ◽  
...  
Keyword(s):  
Liver Transplant ◽  
Ursodeoxycholic Acid ◽  
Primary Biliary Cholangitis ◽  
Acid Therapy ◽  
Free Survival

scholarly journals Guideline review: British Society of Gastroenterology/UK-PBC Primary Biliary Cholangitis treatment and management guidelines

2019 ◽  
Vol 10 (3) ◽  
pp. 316-319 ◽  
Author(s):  
Jorn C Goet ◽  
Gideon M Hirschfield
Keyword(s):  
Liver Disease ◽  
Disease Management ◽  
Ursodeoxycholic Acid ◽  
British Society ◽  
Primary Biliary Cholangitis ◽  
Obeticholic Acid ◽  
Management Guidelines ◽  
Associated Symptoms ◽  
Key Features ◽  
New Guidelines

New guidelines have been produced for the management of primary biliary cholangitis, an infrequent but nonetheless important autoimmune liver disease. We provide a succient commentary and overview of the key features of disease management that arise from these recent guideline recommendations, with a focus on therapy with licensed agents (ursodeoxycholic acid and obeticholic acid) as well as personalised management of disease complications and associated symptoms.

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