生物学的同等性とバイオアベイラビリティのジャーナル

概要

Comparative Bioavailability of Two Extemporaneous Solid Formulations of Carbamazepine against the Innovator in Mexican Healthy Subjects

Aurigena Antunes de Araujo Ferreira, Gerlane Bernardo Coelho Guerra, Lílian Grace da Silva Solon, Estela Dibildox, Jose Perez-Urizar, Abraham Escobedo-Moratilla, Irma Torres-Roque, Maricela Martinez-Delgado, Juan Ramon Zapata-Morales, Luiz Alberto Lira Soares and Amador Covarrubias-Pinedo

Extemporaneous or off-label prescribing is not illegal and may sometimes be clinically and economically appropriate. However it is associated with a number of clinical, safety and ethical issues. Bioequivalence of these products must be proven before they are used in place of patent medicines. In the present study, a single-center, open, randomized, single-dose, 2-period crossover, 2-sequences pilot assay (two subgroups with n=6) was carried out to evaluate the bioavailability of two extemporaneous capsule of carbamazepine (200 mg): A-Formula® (A); and Formule® (B) in comparison to a tablet of the innovator product Tegretol® (C). Twelve healthy volunteers were randomly assigned to one of two arms to receive one test/reference formulation and following a two week wash-out period they received the other compound. Blood sampling was performed over 72 hours after dosing and levels of carbamazepine were determined by HPLC. Main findings of the study include that peak of plasma carbamazepine was faster following the extemporaneous capsules as compared to reference (Tmax: A: 6.58 h; B: 4.83 h vs 8.25-10.00 h, respectively), although no changes was observed in Cmax (A: 3.32 μg/mL; B: 3.10 μg/mL vs C: 3.14-2.85 μg/mL) neither in AUC0-t (A: 116.34 μg*h/mL; B: 145.66 μg*h/mL vs C: 123.18-138.37 μg*h/mL). The elimination half-life that ranged between 38.64-61.29 h but not difference were observed between all formulations. By using bioequivalence statistics it appears that A-Formula® or Formule® is bioequivalent to Tegretol® in terms of AUC0-t but not regarding Cmax. In conclusion, we demonstrated that two extemporaneous capsules of carbamazepine, A-Formula® and Formule® show similar concentration-time profiles to the reference tablet of immediate Tegretol®, however further studies with longer sample size are needed to confirm its bioequivalence and interchangeability.