Pharmacokinetic Evaluation of Ursodeoxycholic Acid, Unconjugated and Conjugated, within Two Oral Formulations in Healthy Male Subjects

Background: This study aimed to evaluate the bioequivalence (BE) of two oral formulations of ursodeoxycholic acid (UDCA), administered as 300 mg tablets (two tablets; 600 mg total dose), and to assess the pharmacokinetics (PK) and bioequivalence (BE) of UDCA in 24 healthy male subjects. Methods: A Phase I, randomized, open-label, two-period, two-sequence, two-treatment, single-dose crossover study was conducted under fed conditions. Subjects received a 600-mg oral dose of either the test or reference formulation in each period. Plasma PK parameters (Cmax and AUC0-72) for unconjugated and total UDCA were quantified using a validated LC-MS/MS method. Results: The geometric mean ratios (test/reference) and corresponding 90% confidence intervals (CIs) for unconjugated UDCA were: Cmax: 103.42% (90.34% - 118.40%), AUC0-t: 105.09% (94.95% - 116.30%). For total UDCA (conjugated + unconjugated), the results were: Cmax: 100.27% (89.50% - 112.33%), AUC0-72: 96.96% (80.49% - 116.80%). The PK profiles of the test and reference formulations were similar, as demonstrated by the 90% CIs of Cmax and AUC0-72 parameters falling within the accepted BE range of 80% - 125%. Conclusions: Baseline-corrected Cmax and AUC0-72 for unconjugated and total UDCA met the regulatory criteria for bioequivalence. The test formulation is therefore bioequivalent to the reference formulation. No adverse events were reported.