William R. Pritchard Veterinary Medical Teaching Hospital, University of California, Davis CA 95616, USA.
Kenneth L. Maddy Equine Analytical Chemistry Laboratory, School of Veterinary Medicine, University of California, Davis, CA, USA.
Vet J. 2020 Mar;257:105446. doi: 10.1016/j.tvjl.2020.105446. Epub 2020 Feb 21.
To the authors' knowledge, there have been no studies evaluating the pharmacokinetics of chloramphenicol administered orally to horses at the currently recommended dose of 50 mg/kg PO q6 h for multiple days. The published antimicrobial susceptibility breakpoint is 8.0 ug/mL; it is unknown if this concentration is achievable at the recommended dose rate in horses. The aim of this prospective multi-dose pharmacokinetic study was to perform pharmacokinetic analysis of chloramphenicol after multiple doses. The authors hypothesize that the antimicrobial susceptibility breakpoint will not be reached. Seven healthy adult horses were administered 50 mg/kg chloramphenicol base tablets PO q6 h for 4 days. Blood was collected via venipuncture daily at 4 and 6 h after administration for the first 15 doses. After the 16th dose, an IV catheter was aseptically placed in the right jugular vein and blood was collected at regular intervals for pharmacokinetic analysis. Maximum chloramphenicol concentration was variable between horses (2.1-42.7 μg/mL). The highest average chloramphenicol concentration was just below the susceptibility breakpoint at 7.7 ug/mL while the lowest was well below the breakpoint at 1.5 ug/mL. On average, the time above 8.0 μg/mL was 75 min, considerably less than the recommended 50% of the dosing interval. When chloramphenicol is administered at a dose of 50 mg/kg PO q6 h in horses, the highest reliably achievable steady state concentration for at least half of the dosing interval is 2.0 μg/mL. The established susceptibility breakpoint of 8.0 ug/mL is not achievable in adult horses, and should be re-evaluated.
据作者所知，目前尚无研究评估马每 6 小时口服 50 毫克/千克，连续多日给予氯霉素的药代动力学。已公布的抗菌药敏折点为 8.0ug/ml；尚不清楚在推荐剂量下该浓度是否可在马中达到。本前瞻性多剂量药代动力学研究旨在对多次给药后的氯霉素进行药代动力学分析。作者假设抗菌药敏折点不会达到。7 匹健康成年马每 6 小时口服 50 毫克/千克氯霉素碱片，连续 4 天。前 15 剂给药后 4 小时和 6 小时通过静脉穿刺每天采集血液。第 16 剂后，右颈静脉无菌放置静脉导管，定期采集血液进行药代动力学分析。马之间最大氯霉素浓度差异很大（2.1-42.7μg/ml）。最高平均氯霉素浓度略低于药敏折点 7.7ug/ml，而最低浓度明显低于药敏折点 1.5ug/ml。平均而言，浓度高于 8.0μg/ml 的时间为 75 分钟，远低于推荐的 50%给药间隔。当马以 50 毫克/千克 PO 每 6 小时给予氯霉素时，至少一半给药间隔内可达到的最高稳态浓度为 2.0μg/ml。8.0ug/ml 的既定药敏折点在成年马中无法达到，应重新评估。
