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硫糖铝对健康犬口服米诺环素吸收的影响。

Effect of sucralfate on oral minocycline absorption in healthy dogs.

作者信息

KuKanich K, KuKanich B, Harris A, Heinrich E

机构信息

Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, Manhattan, KS, USA.

出版信息

J Vet Pharmacol Ther. 2014 Oct;37(5):451-6. doi: 10.1111/jvp.12116. Epub 2014 Mar 10.

DOI:10.1111/jvp.12116
PMID:24611544
Abstract

Sucralfate and minocycline may be administered concurrently to dogs. The relative bioavailability of tetracyclines may be reduced if administered with sucralfate, but studies confirming these interactions in dogs are not available. This study evaluated the pharmacokinetics of oral minocycline in dogs (M), determined the effects of concurrent administration of sucralfate and minocycline (MS) on minocycline pharmacokinetics, determined the effects of delaying sucralfate administration by 2 h (MS+2) on minocycline pharmacokinetics, and established dosing recommendations based on pharmacodynamic indices. Oral minocycline (300 mg) and sucralfate suspension (1 g) were administered to five greyhounds in a randomized crossover design. Minocycline plasma concentrations were evaluated using liquid chromatography with mass spectrometry. The maximum plasma concentration (CMAX ) and area under the curve (AUC) of minocycline were 1.15 μg/mL and 8.0 h* μg/mL, respectively. The CMAX and AUC were significantly lower (P < 0.05) in the MS group (CMAX  = 0.33 μg/mL, AUC 3.0 hμg/mL) compared with M or MS+2 (CMAX = 0.97 μg/mL, AUC 10.3 hμg/mL). Delaying sucralfate by 2 h did not decrease oral minocycline absorption, but concurrent administration significantly decreased minocycline absorption. A dose of 7.5 mg/kg p.o. q12 h achieves the pharmacodynamic index for a bacterial minimum inhibitory concentration (MIC) of 0.25 μg/mL (AUC:MIC≥33.9).

摘要

硫糖铝和米诺环素可同时给犬使用。若与硫糖铝同时给药,四环素的相对生物利用度可能会降低,但尚无在犬身上证实这些相互作用的研究。本研究评估了犬口服米诺环素的药代动力学(M组),确定了同时给予硫糖铝和米诺环素(MS组)对米诺环素药代动力学的影响,确定了将硫糖铝给药延迟2小时(MS + 2组)对米诺环素药代动力学的影响,并根据药效学指标制定了给药建议。采用随机交叉设计,给5只灵缇犬口服米诺环素(300毫克)和硫糖铝混悬液(1克)。使用液相色谱 - 质谱联用仪评估米诺环素的血浆浓度。米诺环素的最大血浆浓度(CMAX)和曲线下面积(AUC)分别为1.15微克/毫升和8.0小时微克/毫升。与M组或MS + 2组(CMAX = 0.97微克/毫升,AUC 10.3小时微克/毫升)相比,MS组的CMAX和AUC显著降低(P < 0.05)(CMAX = 0.33微克/毫升,AUC 3.0小时*微克/毫升)。将硫糖铝给药延迟2小时不会降低口服米诺环素的吸收,但同时给药会显著降低米诺环素的吸收。口服剂量为7.5毫克/千克,每12小时一次,可达到针对细菌最低抑菌浓度(MIC)为0.25微克/毫升的药效学指标(AUC:MIC≥33.9)。

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