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

British Journal of Clinical Pharmacology

Volumn 68, Issue 1, 2009, Pages 34-42

  Del Tacca, Mario ^a,b   Pasqualetti, Giuseppe ^a,b   Di Paolo, Antonello ^b   Virdis, Agostino ^b   Massimetti, Gabriele ^b   Gori, Giovanni ^b   Versari, Daniele ^b   Taddei, Stefano ^a,b   Blandizzi, Corrado ^a,b  

^a UNIVERSITY HOSPITAL OF PISA   (Italy)

^b UNIVERSITY OF PISA   (Italy)

Author keywords

Amoxicillin; Bioequivalence; Branded formulation; Generic formulation; Interchangeable drug; Pharmacokinetics

Indexed keywords

AMOXICILLIN; GENERIC DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; BIOEQUIVALENCE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CROSSOVER PROCEDURE; DERMATITIS; DIARRHEA; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; FEMALE; FEVER; HEADACHE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; MALE; MAXIMUM PLASMA CONCENTRATION; NAUSEA; PERIORBITAL EDEMA; PHOTOSENSITIZATION; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SINGLE BLIND PROCEDURE; SINGLE DRUG DOSE; TABLET FORMULATION;

ADULT; AMOXICILLIN; ANTI-BACTERIAL AGENTS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CROSS-OVER STUDIES; DRUGS, GENERIC; FEMALE; HUMANS; ITALY; MALE; SINGLE-BLIND METHOD; TABLETS; THERAPEUTIC EQUIVALENCY; YOUNG ADULT;

EID: 67650938655     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2009.03399.x     Document Type: Article

References (24)

1. The European Agency for the Evaluation of Medicinal Products (EMEA). Note for guidance on the investigation of bioavailability and bioequivalence. 2001. CPMP/EWP/QWP/1401/98. Available at http://www.emea.europa.eu/pdfs/human/ewp/ 140198en.pdf (last accessed 18 December 2008).
2. Department of Health and Human Services Food and Drug Administration (HHS/FDA). Guidance for industry: bioavailability and bioequivalence studies for orally administered drug products - general considerations. 2003. Available at http:/www.fda.gov/cder/guidance/index.htm (last accessed 18 December 2008).
3. World Health Organization (WHO). Multisource (generic) pharmaceutical products: guidelines on registration requirements to establish interchangeability. 2005. Working document QAS/04.093/Rev.4. Available at http://www.who.int/medicines/services/expertcommittees/pharmprep/ QAS04-093Rev4-final.pdf (last accessed 18 December 2008).
4. Meredith P. Bioequivalence and other unresolved issues in generic drug substitution. Clin Ther 2003 25 : 2875 90.
5. Chen ML, Shah V, Patnaik R, Adams W, Hussain A, Conner D, Mehta M, Malinowski H, Lazor J, Huang SM, Hare D, Leske L, Sporn D, Williams R. Bioavailability and bioequivalence: an FDA regulatory overview. Pharm Res 2001 18 : 1645 50.
6. Crawford P, Feely M, Guberman A, Kramer G. Are there potential problems with generic substitution of antiepileptic drugs? A review of issues. Seizure 2006 15 : 165 76.
7. Yu LX, Amidon GL, Polli JE, Zhao H, Mehta MU, Conner DP, Shah VP, Lesko LJ, Chen ML, Lee VH, Hussain AS. Biopharmaceutics Classification System: the scientific basis for biowaiver extensions. Pharm Res 2002 19 : 921 5.
8. World Health Organization (WHO). Proposal to waive in vivo bioequivalence requirements for the WHO model list of essential medicines immediate release, solid oral dosage forms. 2005. Working document QAS/04.109/Rev.1. Available at http://www.who.int/medicines/services/expertcommittees/pharmprep/conf-materials/ en/index.html (last accessed 18 December 2008).
9. The European Agency for the Evaluation of Medicinal Products (EMEA). Concept paper on BCS-based biowaiver. 2007. EMEA/CHMP/EWP/213035/2007. Available at http://www.emea.europa.eu/pdfs/human/ewp/21303507en.pdf (last accessed 18 December 2008).
10. Scaglione F, Paraboni L. Influence of pharmacokinetics/ pharmacodynamics of antibacterials in their dosing regimen selection. Expert Rev Anti Infect Ther 2006 4 : 479 90.
11. Leach AJ, Morris PS, Mathews JD Chronic Otitis Media Intervention Trial - One (COMIT1) Group. Compared to placebo, long-term antibiotics resolve otitis media with effusion (OME) and prevent acute otitis media with perforation (AOMwiP) in a high-risk population: a randomized controlled trial. BMC Pediatr 2008 8 : 23 34.
12. UPS, The United States Pharmacopeia, 24th edn, Rockville, MD : United States Pharmacopeial Convention Inc., 2000.
13. Petri WA. Penicillins, cephalosporins, and other beta-lactam antibiotics. In : The Pharmacological Basis of Therapeutics, 12th edn, ed. Bruton LL. New York, NY : McGraw-Hill, 2006 1127 54.
14. Du X, Li C, Sun HK, Nightingale CH, Nicolau DP. A sensitive assay of amoxicillin in mouse serum and broncho-alveolar lavage fluid by liquid-liquid extraction and reversed-phase HPLC. J Pharm Biomed Anal 2005 5 : 648 52.
15. The European Agency for the Evaluation of Medicinal Products (EMEA). Questions & answers on the bioavailability and bioequivalence guideline. 2007. EMEA/CHMP/ EWP/40326/2006. Available at http://www.emea.europa.eu/pdfs/ human/ewp/4032606en.pdf (last accessed 18 December 2008).
16. The European Agency for the Evaluation of Medicinal Products (EMEA). Recommendation on the need for revision of (CHMP) (Note for guidance on the investigation of bioavailability and bioequivalence). 2007. CPMP/EWP/ QWP/1401/98. EMEA/CHMP/EWP/200943/2007. Available at http://www.emea.europa.eu/ pdfs/human/ewp/20094307en.pdf (last accessed 18 December 2008).
17. Reiffel JA. Issues in the use of generic antiarrhythmic drugs. Curr Opin Cardiol 2001 16 : 23 9.
18. Concia E, Novelli A, Schito GC, Marchese A. Ideal microbiological and pharmacological characteristics of a quality antimicrobial agent: comparing original and generic molecules. J Chemother 2007 6 : 609 19.
19. Elkoshi Z, Behr D, Mirimsky A. Multiple-dose studies can be a more sensitive assessment for bioequivalence than single-dose studies: the case with omeprazole. Clin Drug Invest 2002 22 : 585 92.
20. Murakami K, Okimoto T, Kodama M, Sato R, Watanabe K, Fujioka T. Evaluation of three different proton pump inhibitors with amoxicillin and metronidazole in retreatment for Helicobacter pylori infection. J Clin Gastroenterol 2008 42 : 139 42.
21. Edwards SJ, Lind T, Lundell L. Systematic review: proton pump inhibitors (PPIs) for the healing of reflux oesophagitis - a comparison of esomeprazole with other PPIs. Aliment Pharmacol Ther 2006 24 : 743 50.
22. Hassan-Alin M, Andersson T, Bredberg E, Röhss K. Pharmacokinetics of esomeprazole after oral and intravenous administration of single and repeated doses to healthy subjects. Eur J Clin Pharmacol 2000 56 : 665 70.
23. Verbeeck RK, Kanfer I, Walker RB. Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy. Eur J Pharm Sci 2006 28 : 1 6.
24. Davies G. Changing the salt, changing the drug. Pharm J 2001 266 : 322 3.