Is generic rifaximin still a poorly absorbed antibiotic? A comparison of branded and generic formulations in healthy volunteers.
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-α, whose systemic bioavailability is very limited. This study was performed to compare the pharmacokinetics 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 (2×200mg) 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 urinary samples were collected at preset times (for 24h or 48h, 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 administration of generic rifaximin than after rifaximin-α. 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 formulations of rifaximin. As a consequence, the therapeutic results obtained with rifaximin-α should not be translated sic et simpliciter to the generic formulations of rifaximin, which do not claim containing only rifaximin-α and will display significantly higher systemic absorption in both health and disease.
Division of Pharmacology, Department of Clinical & Experimental Medicine, University of Pisa, Via Roma 55, 56126 Pisa, Italy. Electronic address: corrado.blandizzi@med.unipi.it.
Corrado
C
Blandizzi
Research and Development Division, Alfa Wassermann Pharmaceuticals, Via Ragazzi del' 99 5, 40133 Bologna, Italy. Electronic address: gcviscomi@alfawassermann.it.
Giuseppe Claudio
GC
Viscomi
Institute for Pharmacokinetic and Analytical Studies SA, Via Mastri 36, 6853 Ligornetto, Switzerland. Electronic address: antonio.marzo@ipas-research.com.
Antonio
A
Marzo
Clinical Pharmacology and Digestive Pathophysiology Unit, Department of Clinical and Experimental Medicine, University of Parma, Cattani Pavillon, Maggiore University Hospital, Viale Gramsci 14, 43125 Parma, Italy. Electronic address: scarpi@tin.it.
Carmelo
C
Scarpignato
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D001682:Biological Availability; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008875:Middle Aged; D012294:Rifamycins / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D000078262:Rifaximin; D016037:Single-Blind Method; D055815:Young Adult
D000900:Anti-Bacterial Agents; D016568:Drugs, Generic; D012294:Rifamycins; D000078262:Rifaximin
Bioequivalence; Branded formulation; Generic formulation; Rifaximin; Rifaximin (PubChem CID: 6436173)