Title:Dosage Regimen Formulation and Therapeutic Effect Evaluation of Cyadox Nanosuspension Against Dairy Cow Mastitis Caused by Staphylococcus aureus
Volume: 18
Issue: 7
Author(s): Tingting Yue, Shuyu Xie, Kuiyu Meng, Shenhe Liu, Yuanhu Pan, Wei Qu, ZhenLi Liu and Dongmei Chen*
Affiliation:
- National Reference Laboratory of Veterinary Drug Residues (HZAU) and MOA Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei,China
Keywords:
Cyadox, nanosuspension, mastitis, Staphylococcus aureus (S. aureus), pharmacokinetic and pharmacodynamic
modeling (PK-PD), therapeutic effect.
Abstract:
Aims: In this study, the dosage regimen establishment of cyadox nanosuspension
against dairy cow mastitis caused by Staphylococcus aureus (S. aureus) was used as example to
provide a general reference for the other novel nanocrystal preparations.
Methods: The effect of cyadox against S. aureus isolates from dairy cows were firstly estimated
and then the dosing regimen of nanosuspension after intramammary administration was optimized
according to the model of ex vivo pharmacokinetic (PK) and pharmacodynamic (PD). The therapeutic
efficacy of the predicted dosage regimen was evaluated.
Results: The results demonstrated that cyadox has a concentration-dependent effect on S. aureus.
The smallest and highest values of minimum inhibitory concentration (MIC) against 80 isolates
was 8 and 64 μg/mL, respectively. The corresponding MIC 50 and MIC 90 was 16 and 32 μg/mL,
respectively. The MIC against the pathogenic S. aureus SAHZ156001 in broth and milk were 16
and 32 μg/mL, respectively. The AUC 0-last and C max of cyadox in milk were 4442.877
μg*h/mL and 753.052 μg/mL, respectively. According to the inhibitory sigmoid E max modeling
and dosage equation, the daily doses were predicted 1.6, 6.6, and 12.2 mL/gland to achieve bacteriostatic,
bactericidal, and elimination effects. The dosage internal was daily administration for
continuous three days.
Conclusion: The clinical experiment showed that the efficient rates were 100, 100, and 90.9%, and
the curative rates were 100, 81.8, and 63.6% in 12.2, 6.6 and 1.6 ml/gland groups, respectively. These
results showed that cyadox nanosuspension had a good prospect as intramammary infusion to
cure dairy cow mastitis infected by S. aureus. This study will be helpful for providing reference for
nanocrystal preparation dosage regimen formulation.
