| Reference | [1]. Am J Vet Res. 2020 Nov;81(11):837-877. doi: 10.2460/ajvr.81.11.873.<br />
Comparative pharmacokinetics of intravenous and intramuscular cefquinome sulfate administration in ducklings and goslings.<br />
Cheng P, Feng T, Zhang Y, Li X, Tian L, Wu J, Cheng F, Zeng Y, Chen H, He X, Fu G, Zheng L, Chen H.<br />
OBJECTIVE: To compare the pharmacokinetics of cefquinome sulfate in ducklings and goslings after IV or IM administration of a single dose. ANIMALS: 216 healthy Muscovy ducklings (Cairina moschata) and 216 healthy Sichuan white goslings (Anser cygnoides). PROCEDURES: Ducklings and goslings were each randomly assigned to 3 groups (n = 72/group) that received a single dose (2 mg/kg) of injectable cefquinome sulfate administered IV or IM or of injectable cefquinome sulfate suspension administered IM. Blood samples were collected at various points after drug administration (n = 6 birds/time point). Plasma cefquinome concentrations were measured by high-performance liquid chromatography with UV detection, and pharmacokinetic parameters were calculated with a 2-compartment model method. RESULTS: After IV injection, mean distribution half-life of cefquinome was longer in goslings (0.446 hours) than in ducklings (0.019 hours), whereas volume of distribution at steady state was greater (0.432 vs 0.042 L/kg) and elimination half-life was slower (1.737 vs 0.972 hours). After IM administration of injectable cefquinome sulfate, bioavailability of the drug was higher in goslings (113.9%) than in ducklings (67.5%). After IM administration of injectable cefquinome sulfate suspension, bioavailability was also higher in goslings (123.1%) than in ducklings (96.8%), whereas elimination half-life was slower (6.917 vs 1.895 hours, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: In goslings, IV administration of cefquinome resulted in slower distribution and metabolism of the drug than in ducklings and IM administration resulted in higher bioavailability. The delayed-release effect of the injectable cefquinome sulfate suspension when administered IM was observed only in goslings.<br />
DOI: 10.2460/ajvr.81.11.873 PMID: 33107745 [Indexed for MEDLINE]<br />
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[2]. Front Pharmacol. 2019 Mar 12;10:249. doi: 10.3389/fphar.2019.00249. eCollection 2019.<br />
Microdialysis Determination of Cefquinome Pharmacokinetics in Murine Thigh From Healthy, Neutropenic, and Actinobacillus pleuropneumoniae-Infected Mice.<br />
Zhang L(1), Yao L(1), Kang Z(1), Huang Z(1), Gu X(1), Shen X(1), Ding H(1).<br />
Author information: (1)Guangdong Key Laboratory for Veterinary Drug Development and Safety Evaluation, South China Agricultural University, Guangzhou, China.<br />
This study was aimed at applying microdialysis to explore cefquinome pharmacokinetics in thigh and plasma of healthy, neutropenic, and Actinobacillus pleuropneumoniae-infected mice. The relative recoveries (RRs) were tested in vitro by dialysis and retrodialysis and in vivo by retrodialysis. ICR mice were randomly divided into four groups: H-40 (healthy mice receiving cefquinome at 40 mg/kg), H-160, N-40 (neutropenic mice), and I-40 mg/kg (thigh infected-mice with A. pleuropneumoniae). After cefquinome administration, plasma was collected by retro-orbital puncture and thigh dialysate was collected by using a microdialysis probe with Ringer's solution at a perfusion rate of 1.5 μL/min. Plasma and thigh dialysate samples were assessed by HPLC-MS/MS and analyzed by a non-compartment model. The mean in vivo recoveries in the thigh were 39.35, 38.59, and 37.29% for healthy, neutropenic, and infected mice, respectively. The mean plasma protein-binding level was 16.40% and was independent of drug concentrations. For all groups, the mean values of the free AUCinf in plasma were higher than those in murine thigh, while the elimination T 1/2β for plasma were lower than those for murine thigh. Cefquinome penetration (AUCthigh/AUCplasma) from the plasma to thigh was 0.76, 0.88, 0.47, and 0.98 for H-40, N-40, I-40, and H-160 mg/kg, respectively. These results indicated that infection significantly affected cefquinome pharmacokinetics in murine thigh. In conclusion, we successfully applied a microdialysis method to evaluate the pharmacokinetics of cefquinome in murine thigh of healthy, neutropenic, and A. pleuropneumonia-infected mice and the pharmacokinetics of cefquinome was obviously affected by infection in thigh.<br />
DOI: 10.3389/fphar.2019.00249 PMCID: PMC6422941 PMID: 30914957<br />
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[3]. J Vet Pharmacol Ther. 2020 Sep;43(5):440-447. doi: 10.1111/jvp.12904. Epub 2020 Aug 19.<br />
Effect of ketoprofen co-administration on pharmacokinetics of cefquinome following repeated administration in goats.<br />
Tekeli IO(1), Turk E(1), Durna Corum D(2), Corum O(2), Kirgiz FC(1), Sakin F(1), Uney K(3).<br />
Author information: (1)Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Hatay Mustafa Kemal, Hatay, Turkey. (2)Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Kastamonu, Kastamonu, Turkey. (3)Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Selcuk, Konya, Turkey.<br />
The pharmacokinetics of cefquinome (2 mg/kg every 24 hr for 5 days) was determined following intramuscular administration alone and co-administration with ketoprofen (3 mg/kg every 24 hr for 5 days) in goats. Six goats were used for the study. In the study, the crossover pharmacokinetics design with 20-day washout period was performed in two periods. Plasma concentrations of cefquinome were assayed using high-performance liquid chromatography by ultraviolet detection. The mean terminal elimination half-life (t1/2ʎz ), area under the concentration-time curve (AUC0-24 ), peak concentration (Cmax ), apparent volume of distribution (Vdarea /F), and total body clearance (CL/F) of cefquinome after the administration alone were 4.85 hr, 11.06 hr*µg/ml, 2.37 µg/mL, 1.23 L/kg, and 0.17 L/h/kg after the first dose, and 5.88 hr, 17.01 hr*µg/mL, 3.04 µg/mL, 0.95 L/kg, and 0.11 L/h/kg after the last dose. Ketoprofen significantly prolonged t1/2ʎz of cefquinome, increased AUC0-24 and Cmax , and decreased Vdarea /F and CL/F. Cefquinome exhibited low accumulation after the administration alone and in combination with ketoprofen. These results indicated that ketoprofen prolonged the elimination of cefquinome in goats. The 24-hr dosing intervals at 2 mg/kg dose of cefquinome, which co-administered with ketoprofen, may maintain T> minimum inhibitory concentration (MIC) values above 40% in the treatment of infections caused by susceptible pathogens with the MIC value of ≤0.75 μg/ml in goats with an inflammatory condition.<br />
DOI: 10.1111/jvp.12904 PMID: 32815194 [Indexed for MEDLINE]<br />
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[4]. Vet Res. 2020 Oct 15;51(1):131. doi: 10.1186/s13567-020-00853-2.<br />
Pharmacokinetic and pharmacodynamic integration for optimal dosage of cefquinome against Streptococcus equi subsp. equi in foals.<br />
Lee DH(1), Birhanu BT(1), Lee EB(1), Lee SJ(2), Boby N(1), Park YS(3), Park SC(4).<br />
Author information: (1)Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Bukgu, Daegu, 41566, Republic of Korea. (2)Developmental and Reproductive Toxicology Research Group, Korean Institute of Toxicology, Daejeon, 34114, Republic of Korea. (3)Department of Equine Industry, Korea National College of Agriculture and Fisheries, Jeonju, 54874, Republic of Korea. [email protected]. (4)Laboratory of Veterinary Pharmacokinetics and Pharmacodynamics, College of Veterinary Medicine, Kyungpook National University, Bukgu, Daegu, 41566, Republic of Korea. [email protected].<br />
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 pharmacodynamics 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 chromatography. 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 administered 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.<br />
DOI: 10.1186/s13567-020-00853-2 PMCID: PMC7566116 PMID: 33059768 [Indexed for MEDLINE]<br />
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[5]. Anal Bioanal Chem. 2018 Nov;410(28):7465-7475. doi: 10.1007/s00216-018-1360-8. Epub 2018 Sep 14.<br />
Quantitative analysis of cefquinome considering different matrix compositions of bovine colostrum and raw milk.<br />
Helmschrodt C(1), Schmidt K(2), Bertulat S(3), Klein L(4), Finnah A(2), Heuwieser W(3), Richter A(5).<br />
Author information: (1)Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 15, 04103, Leipzig, Germany. [email protected]. (2)Federal Office of Consumer Protection and Food Safety (BVL), Referat 305 Postfach 110260, 10832, Berlin, Germany. (3)Clinic for Animal Reproduction, Faculty of Veterinary Medicine, Freie Universität Berlin, Königsweg 65, 14163, Berlin, Germany. (4)Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 15, 04103, Leipzig, Germany. (5)Institute of Pharmacology, Pharmacy and Toxicology, Faculty of Veterinary Medicine, University of Leipzig, An den Tierkliniken 15, 04103, Leipzig, Germany. [email protected].<br />
A robust liquid chromatography-tandem mass spectrometry method was developed and comprehensively validated for the quantification of cefquinome considering the changing matrix composition from bovine colostrum to raw milk. Sample preparation consisted of addition of isotopically labeled cefquinome internal standard prior to protein precipitation of 2 g colostrum or milk followed by solid-phase extraction. A wide concentration range from 1 to 5000 ng cefquinome per gram of colostrum or milk was quantified using a 3200 QTRAP tandem mass spectrometer in positive ionization mode with electrospray ionization. Validation was performed according to the European Commission Decision 2002/657/EC guidelines. Matrix-comprehensive in-house validation included analytical limits CCα and CCβ, recovery, precision and calibration curves with prediction intervals, storage conditions, and evaluation of robustness based on factorial effect analysis. The detection limit was 0.2 ng cefquinome per gram of colostrum or milk. Recovery was between 98.4 and 99.4% for cefquinome concentrations from 4 to 240 ng/g. None of the investigated validation factors (matrix, storage of extracts, lot of SPE cartridges, and operators) exerted an influence higher than ± 3.2%, indicating that these factors make relatively low contributions to the respective combined measurement uncertainties. The comprehensively validated method enables routine residue control purposes and to monitor the pharmacokinetics of cefquinome in bovine colostrum and raw milk. In particular, residue depletion curves of cefquinome from high concentrations in first milking after treatment to concentrations far below the maximum residue limit can be measured.<br />
DOI: 10.1007/s00216-018-1360-8 PMID: 30218123 [Indexed for MEDLINE]
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