Pharmacokinetic and bioequivalence comparison between ursodeoxycholicacid tablets 500mg: An open label, balanced, randomized-sequence, singledose,two-period crossover study in healthy male volunteers

This present bioequivalence study was designed to determine the pharmacokinetic, bioavailability and bioequivalence of Ursodeoxycholic Acid 500mg Tablets in comparison with URSO FORTETM Ursodiol 500mg Tablets after single dose administration under fed conditions in healthy adult male subjects. Therefore the design of an open label, balanced, randomized, two-sequence, single dose, two way crossover study with a wash-out period of at least 7 days was used. An open-labeled, balanced, single-dose with food, two-treatment, two-period, twosequence, randomized crossover study was conducted in 12 healthy male volunteers. Each volunteer received a 500mg tablet of the reference or test drug respectively. On the day of dosing, blood samples were collected before dosing and at various time points up to 24 hours after dosing. Analysis of Ursodeoxycholic Acid concentrations was performed using a validated liquid chromatography with tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the noncompartmental model. Drug safety and tolerability were assessed. The pharmacokinetic parameters including Cmax, AUC0-t, AUC0-inf, Tmax, t1/2 and Kel were analyzed using the non-compartmental model. Drug safety and tolerability were assessed. The primary pharmacokinetic parameters (Cmax, AUC0-t and AUC0-inf) 90%CI were within the 80 to 125% interval required for bioequivalence as stipulated in the current regulations of the USFDA acceptance criteria. The geometric mean ratios (Test/Reference) between the two products of 500mg tablets under fed condition were 111.69% (91.86%-119.53%) for Cmax ratios, 88.84% (85.74%-109.49%) for AUC0-t ratios and 92.36% (90.49%-107.97%) for AUC0-inf ratios of Ursodeoxycholic Acid. 12 volunteers had completed both treatment periods. There was no significant difference of the Tmax parameter between the two formulations (p >0.05). No serious adverse events related to the study drugs were found. This single dose study found that the test formulation ursodeoxycholic acid 500mg tablets are bioequivalent to the reference formulation URSO FORTETM Ursodiol 500mg Tablets in terms of extent and rate of absorption, under fed condition in healthy adult male volunteers according to the USFDA regulatory guidance.