Synthesis of obeticholic acid, a farnesoid X receptor agonist, and its major metabolites labeled with deuterium

Gai, Kuo; Huang, Yu; Li, Baomin; Zhang, Yinsheng

doi:10.1002/jlcr.3643

Cited by 1 publication

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“…16 The main active metabolites are Glyco-OCA and Tauro-OCA. 17 The AUC 0-∞ of OCA could not be calculated completely because OCA is subject to enterohepatic circulation, the PK parameters of the active metabolites, Glyco-OCA and Tauro-OCA were used as supporting data in this…”

Section: Discussionmentioning

confidence: 99%

Bioequivalence and Pharmacokinetic Profiles of Generic and Branded Obeticholic Acid in Healthy Chinese Subjects Under Fasting and Fed Conditions

Wang¹,

Yu²,

Li³

et al. 2021

DDDT

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This study was conducted to evaluate the bioequivalence (BE) of a generic form of obeticholic acid (OCA) and Ocaliva TM under fasting and fed conditions and to determine the effects of food on the pharmacokinetic (PK) profiles of OCA in healthy Chinese subjects. Methods: A randomized, single-dose, three-sequence, three-period, partial replicated crossover study was conducted with a 21-day washout interval between periods under fasting (n=48) and fed (n=48) conditions. Blood samples for OCA and its metabolites Glyco-OCA and Tauro-OCA were collected up to 168 hours after administration in each period. PK parameters were calculated using the non-compartmental method. Geometric mean ratios for PK parameters of the test to reference drug under fasting and fed conditions and their 90% confidence intervals were estimated. Safety evaluations were carried out all through the study. Results: A total of 91 subjects completed the study with 45 in a fasted state and 46 receiving a high-fat diet. There were no serious or unexpected drug-related adverse events occurring during the study. There was no significant difference in the main PK parameters of the two preparations, irrespective of the fasting or fed conditions. Under fasting and fed conditions, the S WR of lnC max , lnAUC 0-t and lnAUC 0-∞ were 0.445, 0.370, 0.448, 0.340, 0.168, and 0.180, respectively. Thus, the average BE or the reference-scaled average BE was used to verify that the two preparations were bioequivalent under fasting and fed conditions. Compared with the fasting state, the AUC 0-t of the test drug, the AUC 0-t , and AUC 0-∞ of the reference drug were higher in the fed state. Conclusion:The test drug and the reference drug were BE and well tolerated in Chinese healthy subjects under both fasting and fed conditions. Food-intake may cause a significant difference in the main PK parameters of the two preparations.

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Section: Discussionmentioning

confidence: 99%

Bioequivalence and Pharmacokinetic Profiles of Generic and Branded Obeticholic Acid in Healthy Chinese Subjects Under Fasting and Fed Conditions

Wang¹,

Yu²,

Li³

et al. 2021

DDDT

View full text Add to dashboard Cite

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Synthesis of obeticholic acid, a farnesoid X receptor agonist, and its major metabolites labeled with deuterium

Abstract: Simple and facile methods for the synthesis of deuterium-labeled obeticholic acid and its 2 metabolites, glycine and taurine conjugates of obeticholic acid, are described herein. The 3 deuterated compounds were applicable for use as internal standards in drug development.

Cited by 1 publication

References 4 publications

Bioequivalence and Pharmacokinetic Profiles of Generic and Branded Obeticholic Acid in Healthy Chinese Subjects Under Fasting and Fed Conditions

Bioequivalence and Pharmacokinetic Profiles of Generic and Branded Obeticholic Acid in Healthy Chinese Subjects Under Fasting and Fed Conditions

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