Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach

Autor: Peter Damborg, Julie Melsted Birch, Amir Atabak Ronaghinia, Henrik Lauritz Frandsen, Tina Struve, Pierre-Louis Toutain
Přispěvatelé: Innovations Thérapeutiques et Résistances (InTheRes), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Veterinary Research
Veterinary Research, BioMed Central, 2021, 52 (1), pp.34. ⟨10.1186/s13567-021-00906-0⟩
Ronaghinia, A A, Birch, J M, Frandsen, H L, Toutain, P L, Damborg, P & Struve, T 2021, ' Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison ) : a pharmacokinetic-pharmacodynamic approach ', Veterinary Research, vol. 52, no. 1, 34 . https://doi.org/10.1186/s13567-021-00906-0
Veterinary Research, Vol 52, Iss 1, Pp 1-16 (2021)
Ronaghinia, A A, Birch, J M, Frandsen, H L, Toutain, P-L, Damborg, P & Struve, T 2021, ' Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison) : a pharmacokinetic-pharmacodynamic approach ', Veterinary Research, vol. 52, no. 1, 34 . https://doi.org/10.1186/s13567-021-00906-0
ISSN: 0928-4249
1297-9716
DOI: 10.1186/s13567-021-00906-0⟩
Popis: Staphylococcus delphini is one of the most common pathogens isolated from mink infections, especially dermatitis. Tylosin (TYL) is used frequently against these infections, although no evidence-based treatment regimen exists. This study aimed to explore the dosage of TYL for infections caused by S. delphini in mink. Two animal experiments with a total of 12 minks were conducted to study the serum pharmacokinetic (PK) characteristics of TYL in mink after 10 mg/kg IV and oral dosing, respectively. The concentration of TYL in serum samples collected before and eight times during 24 h after TYL administration was quantitated with liquid chromatography quadrupole time-of-flight mass spectrometry, and the TYL disposition was analyzed using non-linear mixed effect analysis. The pharmacodynamics (PD) of TYL against S. delphini were studied using semi-mechanistic modeling of in vitro time-kill experiments. PKPD modeling and simulation were done to establish the PKPD index and dosage regimen. The disposition of TYL was described by a two-compartmental model. The area under the free concentration–time curve of TYL over the minimum inhibitory concentration of S. delphini (fAUC/MIC) was determined as PKPD index with breakpoints of 48.9 and 98.7 h for bacteriostatic and bactericidal effect, respectively. The calculated daily oral dose of TYL was 2378 mg/kg, which is 238-fold higher than the currently used TYL oral dosage regimen in mink (10 mg/kg). Accordingly, sufficient TYL concentrations are impossible to achieve in mink plasma, and use of this drug for extra-intestinal infections in this animal species must be discouraged.
Databáze: OpenAIRE
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