Lack of pharmacokinetic bioequivalence between generic and branded amoxicillin formulations. A post-marketing clinical study on healthy volunteers.
OBJECTIVE
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 C(max) 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 C(max) on the basis of single-dose pharmacokinetic assessment.
Del Tacca
Mario
M
Clinical Pharmacology Centre for Drug Experimentation, Pisa University Hospital, Pisa, Italy. deltacca@med.unipi.it
Pasqualetti
Giuseppe
G
Di Paolo
Antonello
A
Virdis
Agostino
A
Massimetti
Gabriele
G
Gori
Giovanni
G
Versari
Daniele
D
Taddei
Stefano
S
Blandizzi
Corrado
C
D000328:Adult; D000658:Amoxicillin / Q000493:pharmacokinetics* / Q000592:standards; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000592:standards; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D016568:Drugs, Generic / Q000493:pharmacokinetics* / Q000592:standards; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D016037:Single-Blind Method; D013607:Tablets; D013810:Therapeutic Equivalency; D055815:Young Adult
D000900:Anti-Bacterial Agents; D016568:Drugs, Generic; D013607:Tablets; D000658:Amoxicillin