Bioequivalence Study of Two Formulations of Ibandronic Acid 150-mg Film-Coated Tablets in Healthy Volunteers Under Fasting Conditions: A Randomized, Open-Label, Three-Way, Reference-Replicated Crossover Study

摘要

Aims This bioequivalence study aimed to compare rate and extent of absorption of a generic medicinal product of ibandronic acid 150-mg film-coated tablet versus Bonviva?. Methods This was a single-centre, open-label, randomized, three-way, three-sequence, reference-replicated, crossover bioequivalence study, under fasting conditions. A single oral dose of ibandronic acid as one 150-mg film-coated tablet was administered in each study period. Each washout period lasted 14?days. Blood samples were collected according to a predefined sampling schedule and up to 48.0?hours after administraton in each period. Plasma concentrations of ibandronic acid were measured using a liquid chromatograph–mass spectrometry/mass spectrometry method. Bioequivalence between generic and reference medicinal products is acceptable if the 90?% confidence intervals (CI) of ratio of least-squares means between the test and the reference product of ln-transformed area under the serum concentration–time curve from time zero to time of last measurable concentration (AUC_{0– t} ) is within the 80.00–125.00?% interval. Prospectively, a scaled average bioequivalence approach for maximum serum concentration ( C _max) was established. Results 153 healthy volunteers were enrolled and randomized. After the test formulation ( T ) and first and second Bonviva? ( R ) dosing, the C _max was 96.71?±?90.19?ng/mL, 92.67?±?91.48?ng/mL and 87.94?±?60.20?ng/mL and the AUC_{0– t} was 390.83?±?287.27?ng·h/mL, 388.54?±?356.76?ng·h/mL and 383.53?±?246.72, respectively. Ratios of T / R and 90?% CI were 100.92?% (94.35–107.94) for AUC_{0– t} , 100.90?% (94.37–107.88) for AUC_0–inf and 102.56?% (95.05–110.67) for C _max. Conclusions Test formulation of ibandronic acid is bioequivalent in rate and extent of absorption to Bonviva? following a 150-mg dose, under fasting conditions.