Estudio de biodisponibilidad comparativa de Binap® (ibrutinib 140 mg) de Laboratorio Varifarma S.A. respecto al producto de referencia Imbruvica®.

Ibrutinib is an antineoplastic drug indicated for the treatment of mantle cell lymphoma and chronic lymphocytic leukemia. The therapeutic activity of ibrutinib is exerted by a highly specific reduction in the activity of Bruton's tyrosine kinase, a key player in the progression of certain tumors. Here we report the bioequivalence study of Binap®, a new formulation of ibrutinib 140 mg, manufactured by Laboratorio Varifarma S.A., with respect to the reference product Imbruvica® 140 mg, manufactured by Janssen Cilag Farmaceutica S.A. The clinical trial consisted of an open-label single administration of a 140 mg dose of ibrutinib, under fasting conditions, in 36 healthy male volunteers. A two-sequence, four-period (2 x 4) crossover replicate design was followed,with a 7-day washout period between each treatment period. Ibrutinib plasma concentration was quantified by means of a validated bioanalytical methodology using high performance liquid chromatography coupled to a tandem triple quadrupole mass spectrometry detector (HPLC-MS / MS). The results obtained in this study indicate that when a single 140 mg dose is administered to healthy subjects, both formulations show, on average, practically identical pharmacokinetic profiles. The pharmacokinetic parameters evaluated in this study were maximum plasma concentration (Cmax), area under the pharmacokinetic curve to the last sample obtained and extrapolated to infinity (AUC0-T and AUC0-∞), time to reach maximum plasma concentration (Tmax), elimination half life (T1/2) and elimination constant (Kel). The statistical data analysis for demonstration of bioequivalence was conducted on Cmax, AUC0-T and AUC0-∞, according to national and international bioequivalence regulations, with a confidence interval of 90% (CI90%). The analysis of variance test (ANOVA) with logarithmically transformed data shows a similar intra-subject CV for both products, 60% for Cmax and 46% for AUC0-T. For the parameter AUC0-T the point estimate is 96.4% (IC90% from 85.4 to 108.9%), for AUC0-∞ the point estimate is 99.4% (IC90% from 88.7 to 111, 4%), both within the pre-established bioequivalence range of 80-125%, and for Cmax the point estimate is 85.1% (IC90% from 72.2 to 100.2%), contained within the expanded bioequivalence range of 69.8-143.2%, according to the intra-subject CV obtained (> 50%). The results of this study indicate that Binap® (ibrutinib 140 mg) manufactured by Laboratorios Varifarma S.A. is bioequivalent to Imbruvica® 140 mg from Janssen Cilag S.A., therefore both products may be considered interchangeable in medical practice.