Pharmacokinetic and pharmacodynamic integration for optimal dosage of cefquinome against Streptococcus equi subsp. equi
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RESEARCH ARTICLE
Open Access
Pharmacokinetic and pharmacodynamic integration for optimal dosage of cefquinome against Streptococcus equi subsp. equi in foals Dong‑Ha Lee1, Biruk Tesfaye Birhanu1, Eon‑Bee Lee1, Seung‑Jin Lee2, Naila Boby1, Yong‑Soo Park3* and Seung‑Chun Park1*
Abstract Cefquinome is administered in horses for the treatment of respiratory infection caused by Streptococcus equi subsp. zooepidemicus, and septicemia caused by Escherichia coli. However, there have been no attempts to use cefquinome against Streptococcus equi subsp. equi (S. equi), the causative agent of strangles. Hence the objective of this study was to calculate an optimal dosage of cefquinome against S. equi based on pharmacokinetics and pharmacodynam‑ ics integration. Cefquinome (1.0 mg/kg) was administered by intravenous and intramuscular routes to six healthy thoroughbred foals. Serum cefquinome concentrations were determined by high-performance liquid chromatogra‑ phy. The in vitro and ex vivo antibacterial activity were determined from minimum inhibitory concentrations (MIC) and bacterial killing curves. The optimal dosage was calculated from the integration of pharmacokinetic parameters and area under the curve (AUC24h/MIC) values. Total body clearance and volume of distribution of cefquinome after intravenous administration were 0.06 L/h/kg and 0.09 L/kg, respectively. Following intramuscular administration, a maximum concentration of 0.73 μg/mL at 1.52 h (Tmax) and a systemic bioavailability of 37.45% were observed. The MIC of cefquinome against S. equi was 0.016 μg/mL. The ex vivo AUC24h/MIC values representing bacteriostatic, and bactericidal activity were 113.11, and 143.14 h, respectively. Whereas the %T > MIC for bactericidal activity was 153.34%. In conclusion, based on AUC24h/MIC values and pharmacokinetic parameters, cefquinome when adminis‑ tered by intramuscularly at a dosage of 0.53 mg/kg every 24 h, would be effective against infection caused by S. equi in foals. Further studies may be necessary to confirm its therapeutic efficacy in a clinical environment. Keywords: cefquinome, Streptococcus equi subsp. equi, antibacterial activity, PK/PD integration, optimal dosage Introduction Cefquinome is a fourth-generation amino-thiazolyl cephalosporin used solely in veterinary medicine [1–3]. The chemical modifications of the basic cephalosporin structure provide cefquinome’s zwitterionic property that *Correspondence: [email protected]; [email protected] 1 Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Bukgu, Daegu 41566, Republic of Korea 3 Department of Equine Industry, Korea National College of Agriculture and Fisheries, Jeonju 54874, Republic of Korea Full list of author information is available at the end of the article
facilitates its rapid penetration across Gram-negative outer membranes, including the porins of the bacterial cell wall and broaden the antimicrobial activity spectrum compared with previous generation cephalosporins
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