Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison): a pharmacokinetic-pharmacodynamic approach
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Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison) : a pharmacokinetic-pharmacodynamic approach. / Ronaghinia, Amir Atabak; Birch, Julie Melsted; Frandsen, Henrik Lauritz; Toutain, Pierre Louis; Damborg, Peter; Struve, Tina.
In: Veterinary Research, Vol. 52, No. 1, 34, 2021.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Evaluating a tylosin dosage regimen for treatment of Staphylococcus delphini infection in mink (Neovison vison)
T2 - a pharmacokinetic-pharmacodynamic approach
AU - Ronaghinia, Amir Atabak
AU - Birch, Julie Melsted
AU - Frandsen, Henrik Lauritz
AU - Toutain, Pierre Louis
AU - Damborg, Peter
AU - Struve, Tina
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1186/s13567-021-00906-0
DO - 10.1186/s13567-021-00906-0
M3 - Journal article
C2 - 33640030
AN - SCOPUS:85101822005
VL - 52
JO - Veterinary Research
JF - Veterinary Research
SN - 0928-4249
IS - 1
M1 - 34
ER -
ID: 258897643