Short Communication Post-marketing surveillance of generic amoxicillin using a microbiological assay and pharmacokinetic approach in rats Livia I.S. de Mattos a , Fausto K. Ferraris a , Tiago S.C. Machado a , Thais M. de Brito a , Amanda S. Chaves a , Heliana F. Martins b , Douglas P. Pinto b , Diego M.D. da Silva b , Fabio C. Amendoeira a, * ,1 a Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, (INCQS/Fiocruz), Av. Brasil, 4365—Manguinhos, Rio de Janeiro, RJ 21040- 900, Brazil b Laboratório de Farmacocinética, Fundação Oswaldo Cruz (Fiocruz), Manguinhos, Rio de Janeiro, RJ, Brazil ARTICLE INFO Article history: Received 30 June 2016 Accepted 15 September 2016 Keywords: Amoxicillin Pharmacokinetics Bioavailability Bioequivalence Quality control Rats A B ST R AC T Generic medicines were developed to increase population access to health treatment, to reduce costs and to allow drugs with the same outcomes to be purchased at lower prices. They are therapeutically equivalent to their brand-name counterparts and are interchangeable with them. However, the accep- tance of generic medicines by physicians and general consumers is often affected by distrust related to quality and efficacy. In this study three different brands of generic amoxicillin were tested. The results showed that two of them were indistinguishable from the innovator in terms of microbiological potency; however, generic B was unable to reach the Brazilian Pharmacopoeia specifications for potency limits. In contrast, generic B was bioequivalent to the innovator amoxicillin in pharmacokinetic assessment and, surprisingly, generic A, which was approved in the microbiological potency assay, lacked pharmacoki- netic equivalence compared with the innovator. Both tests, when used singly, may not be effective at detecting quality deviations in antimicrobial medicines, which indicates that pharmacokinetic tests in rats in association with microbiological potency assays are a valuable tool for post-marketing surveil- lance of generic antibiotics. © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. 1. Introduction Generic drugs are medicines that are therapeutically equiva- lent to a brand-name counterpart and can be interchanged with it. The World Health Organization (WHO) defines these products as therapeutically equivalent if their efficacy and safety are essential- ly the same at the same molar dose. Equivalence has to be determined from appropriate bioequivalence, pharmacodynamic, clinical or in vitro studies [1]. The main goal of developing generic medicines is to promote the accessibility of various populations to lower-priced medicines and to increase adherence to health treatment. Studies have indicated that government efforts to provide lower- cost treatments have been insufficient. The main barrier in low- and middle-income countries is an overall lack of knowledge about ge- nerics and the perception of many patients and physicians that generic medicines are of inferior quality [2]. In addition, a study evaluated consumer perceptions of generic prescriptions and showed that most of the population believes that this type of drug is riskier than the innovator. This line of thought is based on the knowl- edge that the consequences of an unsuccessful treatment are more severe when the medical condition is more serious [3]. Infectious diseases are still among the most common diagno- ses in primary care, and antibiotics such as amoxicillin are used globally in the public health sector to treat bacterial infections [4–6]. Antibiotics with low quality can lead to weak treatment out- comes, thereby increasing the recrudescence potential and promoting the development of antibiotic-resistant bacteria [7]. A recent survey conducted by the Brazilian Health Surveillance Agency showed that three different brands of marketed amoxicillin presenting quality deviations have been commercially suspended [8]. Quality assessment of antibiotics in developing countries is often a two-stage process. The first stage involves drug screening, which is composed of four basic tests: visual inspection; tablet/capsule dis- integration; colorimetric tests; and thin-layer chromatography. The second stage involves identifying all of the compounds present in a sample using a high-performance liquid chromatography (HPLC) * Corresponding author. Laboratory of Pharmacology, Department of Pharmacology and Toxicology, Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Av. Brasil, 4365—Manguinhos, Rio de Janeiro, RJ 21040-900, Brazil. E-mail address: fabio.amendoeira@incqs.fiocruz.br (F.C. Amendoeira). 1 Present address: Laboratory of Pharmacology, Department of Pharmacology and Toxicology, Instituto Nacional de Controle de Qualidade em Saúde, Fundação Oswaldo Cruz, Av. Brasil, 4365—Manguinhos, Rio de Janeiro, RJ 21040-900, Brazil. http://dx.doi.org/10.1016/j.ijantimicag.2016.09.019 0924-8579/© 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved. International Journal of Antimicrobial Agents ■■ (2016) ■■–■■ ARTICLE IN PRESS Please cite this article in press as: Livia I.S. de Mattos, et al., Post-marketing surveillance of generic amoxicillin using a microbiological assay and pharmacokinetic approach in rats, International Journal of Antimicrobial Agents (2016), doi: 10.1016/j.ijantimicag.2016.09.019 Contents lists available at ScienceDirect International Journal of Antimicrobial Agents journal homepage: www.elsevier.com/locate/ijantimicag Q2 Q1 Q3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88