Lack of pharmacokinetic bioequivalence between generic and branded amoxicillin formulations. A post‐marketing clinical study on healthy volunteers

• Published in: British journal of clinical pharmacology 2009-07, Vol.68 (1), p.34-42
• Main Authors: Del Tacca, Mario, Pasqualetti, Giuseppe, Di Paolo, Antonello, Virdis, Agostino, Massimetti, Gabriele, Gori, Giovanni, Versari, Daniele, Taddei, Stefano, Blandizzi, Corrado
• Format: Article
• Language: English
• Subjects: Adult; amoxicillin; Amoxicillin - pharmacokinetics; Amoxicillin - standards; Anti-Bacterial Agents - pharmacokinetics; Anti-Bacterial Agents - standards; bioequivalence; Biological and medical sciences; branded formulation; Chromatography, High Pressure Liquid; Cross-Over Studies; Drugs, Generic - pharmacokinetics; Drugs, Generic - standards; Female; generic formulation; Humans; interchangeable drug; Italy; Male; Medical sciences; Pharmacokinetics; Pharmacology. Drug treatments; Single-Blind Method; Tablets; Therapeutic Equivalency; Young Adult
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/j.1365-2125.2009.03399.x

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Generic medicinal products are ‘copies’ of patented drugs and can be marketed at low cost following patent expiration of the brand‐name preparations. • Although the development of generic medicinal products is regulated by specific guidelines, a number of issues and concerns continue to undermine the confidence of physicians and patients in generic drugs. WHAT THIS STUDY ADDS • The present findings open interesting perspectives for the discussion of the quality of generic drugs in the postmarketing setting. • In particular, our trial shows that postmarketing evaluation of bioequivalence between branded amoxicillin and its generic copies might result in lack of interchangeability. AIMS There are concerns about the quality of generic drugs in the postmarketing setting. The aim was to establish whether two generic formulations of amoxicillin, available on the Italian market, fulfil the criteria for clinical pharmacokinetic bioequivalence vs. the branded drug. METHODS Two generic amoxicillin products (generic A and B) were selected among four fast‐release tablet formulations available on the Italian market. Twenty‐four healthy adult volunteers of either sex participated to a single‐dose, randomized, three‐treatment, crossover, single‐blind bioequivalence study designed to compare generic A and B with branded amoxicillin. Plasma samples were collected at preset times for 24 h after dosing, and assayed for amoxicillin levels by high‐performance liquid chromatography. RESULTS Ninety percent confidence intervals of AUC ratios were 0.8238, 1.0502 (ratio 0.9302) and 0.8116, 1.1007 (ratio 0.9452) for generic A and B vs. branded amoxicillin, respectively. Ninety percent confidence intervals of Cmax ratios were 0.7921, 1.0134 (ratio 0.8960) and 0.8246, 1.1199 (ratio 0.9610) for generic A and B vs. branded amoxicillin, respectively. The mean pharmacokinetic profiles showed that the AUC value of branded amoxicillin was 8.5 and 5.4% greater than that estimated for generic A and B, respectively. Few adverse events were recorded; these were not serious and occurred without apparent relationship to any specific amoxicillin formulation. CONCLUSIONS These results indicate that one of the two marketed amoxicillin generics analysed in the present study is not bioequivalent to the brand leader product for Cmax on the basis of single‐dose pharmacokinetic assessment.