{"title":"美洛昔康对头孢醌在内毒素中毒绵羊体内药动学的影响。","authors":"Muhittin Uslu, Orhan Corum, Enver Yazar","doi":"10.1002/vms3.70462","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study was to investigate the effect of meloxicam on the pharmacokinetics of cefquinome in experimental endotoxemic sheep. In addition, the MIC of cefquinome was determined against Escherichia coli, Pasteurella multocida, Klebsiella pneumoniae, and Mannheimia haemolytica.</p><p><strong>Methods: </strong>The study was carried out on six sheep in three periods according to a longitudinal pharmacokinetic design. Cefquinome (2.5 mg/kg, IV, CFQ) was administered in the first period, cefquinome+meloxicam (1 mg/kg, IV, CFQ+MLX) in the second period, and lipopolysaccharide (20 µg/kg, IV, LPS+CFQ+MLX)+meloxicam+cefquinome in the third period. Plasma cefquinome concentrations were assayed using HPLC-UV, and pharmacokinetic data were calculated by a two-compartment open model.</p><p><strong>Results: </strong>Following a single IV injection of cefquinome, the t<sub>1/2β</sub>, V<sub>dss</sub>, and Cl<sub>T</sub> values were 1.12 h, 0.21 L/kg, and 0.17 L/h/kg, respectively. The t<sub>1/2β</sub> was prolonged from 1.12 to 2.79 h in the LPS+CFQ+MLX group. While V<sub>dss</sub> was increased (from 0.21 to 0.36 L/kg) in the LPS+CFQ+MLX group, Cl<sub>T</sub> decreased (from 0.17 to 0.10 L/h/kg) in the CFQ+MLX and LPS+CFQ+MLX groups. The MICs of cefquinome were 0.031 to 0.063 µg/mL for E. coli, M. haemolytica, and K. pneumoniae and 0.016 to 1 µg/mL for P. multocida. At a 12 h dosing interval, the CFQ, CFQ+MLX, and LPS+CFQ+MLX groups attained a T > MIC ratio of 40% for bacteria with MIC values of ≤ 0.50, ≤ 1, and ≤ 1 µg/mL, respectively.</p><p><strong>Conclusion: </strong>These results indicate that combined administration of meloxicam alters the pharmacokinetics and therapeutic efficacy of cefquinome in experimental endotoxemic sheep.</p>","PeriodicalId":23543,"journal":{"name":"Veterinary Medicine and Science","volume":"11 5","pages":"e70462"},"PeriodicalIF":1.7000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409652/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effect of Meloxicam on the Pharmacokinetics of Cefquinome in Endotoxemic Sheep.\",\"authors\":\"Muhittin Uslu, Orhan Corum, Enver Yazar\",\"doi\":\"10.1002/vms3.70462\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>The objective of this study was to investigate the effect of meloxicam on the pharmacokinetics of cefquinome in experimental endotoxemic sheep. In addition, the MIC of cefquinome was determined against Escherichia coli, Pasteurella multocida, Klebsiella pneumoniae, and Mannheimia haemolytica.</p><p><strong>Methods: </strong>The study was carried out on six sheep in three periods according to a longitudinal pharmacokinetic design. Cefquinome (2.5 mg/kg, IV, CFQ) was administered in the first period, cefquinome+meloxicam (1 mg/kg, IV, CFQ+MLX) in the second period, and lipopolysaccharide (20 µg/kg, IV, LPS+CFQ+MLX)+meloxicam+cefquinome in the third period. Plasma cefquinome concentrations were assayed using HPLC-UV, and pharmacokinetic data were calculated by a two-compartment open model.</p><p><strong>Results: </strong>Following a single IV injection of cefquinome, the t<sub>1/2β</sub>, V<sub>dss</sub>, and Cl<sub>T</sub> values were 1.12 h, 0.21 L/kg, and 0.17 L/h/kg, respectively. The t<sub>1/2β</sub> was prolonged from 1.12 to 2.79 h in the LPS+CFQ+MLX group. While V<sub>dss</sub> was increased (from 0.21 to 0.36 L/kg) in the LPS+CFQ+MLX group, Cl<sub>T</sub> decreased (from 0.17 to 0.10 L/h/kg) in the CFQ+MLX and LPS+CFQ+MLX groups. The MICs of cefquinome were 0.031 to 0.063 µg/mL for E. coli, M. haemolytica, and K. pneumoniae and 0.016 to 1 µg/mL for P. multocida. At a 12 h dosing interval, the CFQ, CFQ+MLX, and LPS+CFQ+MLX groups attained a T > MIC ratio of 40% for bacteria with MIC values of ≤ 0.50, ≤ 1, and ≤ 1 µg/mL, respectively.</p><p><strong>Conclusion: </strong>These results indicate that combined administration of meloxicam alters the pharmacokinetics and therapeutic efficacy of cefquinome in experimental endotoxemic sheep.</p>\",\"PeriodicalId\":23543,\"journal\":{\"name\":\"Veterinary Medicine and Science\",\"volume\":\"11 5\",\"pages\":\"e70462\"},\"PeriodicalIF\":1.7000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12409652/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Veterinary Medicine and Science\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://doi.org/10.1002/vms3.70462\",\"RegionNum\":3,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"VETERINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Veterinary Medicine and Science","FirstCategoryId":"97","ListUrlMain":"https://doi.org/10.1002/vms3.70462","RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"VETERINARY SCIENCES","Score":null,"Total":0}
Effect of Meloxicam on the Pharmacokinetics of Cefquinome in Endotoxemic Sheep.
Objective: The objective of this study was to investigate the effect of meloxicam on the pharmacokinetics of cefquinome in experimental endotoxemic sheep. In addition, the MIC of cefquinome was determined against Escherichia coli, Pasteurella multocida, Klebsiella pneumoniae, and Mannheimia haemolytica.
Methods: The study was carried out on six sheep in three periods according to a longitudinal pharmacokinetic design. Cefquinome (2.5 mg/kg, IV, CFQ) was administered in the first period, cefquinome+meloxicam (1 mg/kg, IV, CFQ+MLX) in the second period, and lipopolysaccharide (20 µg/kg, IV, LPS+CFQ+MLX)+meloxicam+cefquinome in the third period. Plasma cefquinome concentrations were assayed using HPLC-UV, and pharmacokinetic data were calculated by a two-compartment open model.
Results: Following a single IV injection of cefquinome, the t1/2β, Vdss, and ClT values were 1.12 h, 0.21 L/kg, and 0.17 L/h/kg, respectively. The t1/2β was prolonged from 1.12 to 2.79 h in the LPS+CFQ+MLX group. While Vdss was increased (from 0.21 to 0.36 L/kg) in the LPS+CFQ+MLX group, ClT decreased (from 0.17 to 0.10 L/h/kg) in the CFQ+MLX and LPS+CFQ+MLX groups. The MICs of cefquinome were 0.031 to 0.063 µg/mL for E. coli, M. haemolytica, and K. pneumoniae and 0.016 to 1 µg/mL for P. multocida. At a 12 h dosing interval, the CFQ, CFQ+MLX, and LPS+CFQ+MLX groups attained a T > MIC ratio of 40% for bacteria with MIC values of ≤ 0.50, ≤ 1, and ≤ 1 µg/mL, respectively.
Conclusion: These results indicate that combined administration of meloxicam alters the pharmacokinetics and therapeutic efficacy of cefquinome in experimental endotoxemic sheep.
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Veterinary Medicine and Science is the peer-reviewed journal for rapid dissemination of research in all areas of veterinary medicine and science. The journal aims to serve the research community by providing a vehicle for authors wishing to publish interesting and high quality work in both fundamental and clinical veterinary medicine and science.
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