Is generic rifaximin still a poorly absorbed antibiotic? A comparison of branded and generic formulations in healthy volunteers

a b s t r a c t Rifaximin is an antibiotic, locally acting in the gastrointestinal tract, which may exist in different crystal as well as amorphous forms. The branded rifaximin formulation contains the polymorph rifaximin-, whose systemic bioavailability is very limited. This study was performed to compare the pharmacoki- netics of this formulation with that of a generic product, whose composition in terms of solid state forms of the active pharmaceutical ingredient was found to be different. Two tablets (2 × 200 mg) of branded and generic formulations were given to 24 healthy volunteers of either sex, according to a single-blind, randomized, two-treatment, single-dose, two-period, cross-over design. Plasma and uri- nary samples were collected at preset times (for 24 h or 48 h, respectively) after dosing, and assayed for rifaximin concentrations by high-performance liquid chromatography-mass spectrometry. Rifaximin plasma and urine concentration-time profiles showed relevant differences when generic and branded rifaximin were compared. Most pharmacokinetic parameters were significantly higher after administra- tion of generic rifaximin than after rifaximin-. In particular, the differences for Cmax, AUC and cumulative urinary excretion between the generic formulation and the branded product ranged from 165% to 345%. The few adverse events recorded were not serious and not related to study medications. The results of the present investigation demonstrate different systemic bioavailability of generic and branded formu- lations of rifaximin. As a consequence, the therapeutic results obtained with rifaximin- should not be translated sic et simpliciter to the generic formulations of rifaximin, which do not claim containing only rifaximin- and will display significantly higher systemic absorption in both health and disease.