PRUDENT USE OF FLUOROQUINOLONES IN AVIAN SPECIES: PHARMACOKINETICS OF FLUMEQUINE AND ENROFLOXACIN FOR PK/PD MODELLING IN TURKEY.
Tesi di Dottorato
Data di Pubblicazione:
2015
Citazione:
PRUDENT USE OF FLUOROQUINOLONES IN AVIAN SPECIES: PHARMACOKINETICS OF FLUMEQUINE AND ENROFLOXACIN FOR PK/PD MODELLING IN TURKEY / C. Ferraresi ; tutor: P. Cagnardi; coordinatore: G. Savoini. DIPARTIMENTO DI SCIENZE VETERINARIE PER LA SALUTE, LA PRODUZIONE ANIMALE E LA SICUREZZA ALIMENTARE, 2015 Feb 12. 27. ciclo, Anno Accademico 2014. [10.13130/ferraresi-caterina_phd2015-02-12].
Abstract:
The importance of prudent and rational use of antimicrobial is important, not only to safeguard the efficacy of these drugs in humans and veterinary medicine but, even more so, to prevent the emergence and spread of undesirable resistance phenotypes in zoonotic pathogens as well as in commensal bacteria that can be transmitted between animals and humans.
Even more importance and attention is now given to the prudent use of medically important antimicrobial drugs, referring to those drugs for human therapeutic use.
The fluoroquinolones belong to this category. These are very potent antimicrobials and active against a wide range of pathogenic organisms and are well distributed in the body after administration. This class of antimicrobials has a therapeutic effect on most infections in different organs or tissues. Although it is rare that fluoroquinolones are the only available agent for treatment of a specific infectious disease, fluoroquinolones are important alternative medicinal products for a veterinarian to have as option for treatment. Fluoroquinolones have a unique mechanism of action not related to conventional antimicrobials, and therefore their efficacy should be retained as long as possible.
The avian production increased enormously in the last 50 years and the European Union (EU) is one of the world's top producers in poultry meat and a net exporter of poultry products. In this production, turkeys that is considered a “minor species”, but it is important in the livestock production of Italy. Scarce data exist about the usage of antimicrobial drugs in turkey and even less is known about their efficacy. As the limited number of medicinal products authorized in this species, antimicrobial therapy is frequently carried out with the few products authorized or with drugs “extra-label” used with the consequence of increases of selective pressure and also with the possibility of cross-resistance within the same pharmacological group of compounds.
The studies reported in this thesis aimed to revise the use of fluoroquinolones in turkey to maintain the efficacy and reduce the spread of resistance against E.Coli, the most common zoonotic avian pathogen. Pharmacokinetic(PK)/pharmacodynamics (PD) models are the best tool in order to select optimal dosage regimen. To confirm dosages used at farms and allow the integration of PK/PD data, the plasma concentrations in blood from healthy animals collected during treatment with flumequine and enrofloxacin, were determined.
The first step was to optimize and validate a fast, simple, sensitive, and specific liquid chromatography-mass spectrometry (LC-MS)/MS/MS method suitable for the detection of a wide range of concentrations of fluoroquinolones as those occurring in pharmacokinetic and residue depletion studies from several matrices. The first trial presents a sensitive and reliable confirmatory method for the extraction, identification, quantification of five fluoroquinolones . For the extraction and matrix clean-up of fluoroquinolones residues from all biological matrices, the Quick Easy Cheap Effective Rugged Safe (QuEChERS) methodology was adopted; only for plasma samples acetonitrile was used. The analyses were performed by (LC-MS. LC separation was performed on a C18 Kinetex column (100x2.1 mm, 2.6 µm, Phenomenex, CA, USA) with gradient elution using ammonium acetate solution (10 mM, pH 2.5) and methanol containing 0.1% formic acid. Mass spectrometric identification was done using an LTQ XL ion trap (Thermo Fisher Scientific, CA, USA), with a heated electrospray ionization probe, in positive ion mode. The method was validated according to the European Legislation (decision 2002/657/EC) and EMA guideline (EMA/CVMP/VICH/463202/2009); selectivity, linearity response, true
Tipologia IRIS:
Tesi di dottorato
Keywords:
fluoroquinolones resistance ; pharmacokinetics/pharmacodynamics ; turkey
Elenco autori:
C. Ferraresi
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