Repeated administration of trimethoprim/sulfadiazine in the horse -: pharmacokinetics, plasma protein binding and influence on the intestinal microflora
Repeated administration of trimethoprim/sulfadiazine in the horse -: pharmacokinetics, plasma protein binding and influence on the intestinal microflora
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DOI：
10.1046/j.1365-2885.1999.00183.x
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发表时间：
1999-02-01
影响因子：
1.3
通讯作者：
Ingvast-Larsson, C
中科院分区：
文献类型：
--
作者：
Gustafsson, A;Båverud, V;Ingvast-Larsson, C
6匹健康成年马多次静脉注射甲氧普林/磺胺嘧啶(TMP/SDZ)(2.5 mg/kg TMP和12.5 mg/kg SDZ)和口服(P.O.)作为糊剂(5 mg/kg TMP和25 mg/kg SDZ)。两种制剂每天给药两次，共5天，每隔3周静脉注射一次。和口服给药。观察联合用药对肠道菌群的影响，并测定其血药浓度、药代动力学参数和血浆蛋白结合率。静脉注射后，肠道细菌菌群没有重大变化，也没有胃肠道紊乱的临床证据。TMP/SDZ口服给药。在治疗过程中，大肠菌群数量的最初减少是显著的，尽管在静脉注射之间没有明显的差异。口服给药后，稳态给药间隔内的最小血药浓度(C-minss)、消除半衰期(t(1/2β))和平均滞留时间(MRT)均显著高于静注给药。适用于TMP和SDZ。血浆蛋白结合率SDZ为20%，TMP为35%。口服TMP/SDZ 30 mg/kg，每日两次，以糊剂形式给药，是一种在间隔时间内获得高于MIC(体外最低抑菌浓度)的满意方法。
Six healthy adult horses were given repeated administrations of trimethoprim/sulfadiazine (TMP/SDZ) intravenously (i.v.) (2.5 mg/kg TMP and 12.5 mg/kg SDZ) and orally (p.o.) as a paste (5 mg/kg TMP and 25 mg/kg SDZ). Both formulations were given twice daily for 5 days, with a 3-week interval between i.v. and oral administration. The influence of the drug combination on the intestinal microflora was examined and the plasma concentrations, pharmacokinetic parameters and plasma protein binding were determined. There were no major changes in the bacterial intestinal flora and no clinical evidence of gastrointestinal disturbances following the i.v. and oral TMP/SDZ administration. An initial reduction in the number of coliform bacteria during the treatment was notable, though with no evident difference between i.v. and oral treatment, The minimum concentration during a dose interval at steady state (C-minss), the elimination half-life (t(1/2 beta)) and the mean residence time (MRT) were significantly greater after oral administration compared to i.v. for both TMP and SDZ. The plasma protein binding was measured to be 20% for SDZ and 35% for TMP. Oral administration of TMP/SDZ in a dose of 30 mg/kg given twice daily in the form of paste appeared as a satisfactory method for obtaining plasma levels above MIC (minimum inhibitory concentration in vitro) values during the interdosing interval.