Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Acta Pharmacol Sin. 2011 Oct;32(10):1285-93. doi: 10.1038/aps.2011.78. Epub 2011 Sep 5.
To evaluate the pharmacokinetic interactions between theophylline and antofloxacin in vivo and in vitro.
A randomized, 5-day treatment and 3-way crossover design was documented in 12 healthy subjects. The subjects were orally administered with antofloxacin (400 mg on d 1 and 200 mg on d 2 to 5), theophylline (100 mg twice a day and morning dose 200 mg on d 1 and 5), or theophylline plus antofloxacin. The plasma and urinary pharmacokinetics of antofloxacin and theophylline were characterized after the first and last dose. The effect of antofloxacin on theophylline metabolism was also investigated in pooled human liver microsomes.
The 5-day treatment with antofloxacin significantly increased the area of the plasma concentration-time curve and peak plasma concentration of theophylline, accompanied by a decrease in the excretion of theophylline metabolites. On the contrary, theophylline did not affect the pharmacokinetics of antofloxacin. In vitro studies using pooled human hepatic microsomes demonstrated that antofloxacin was a weak reversible and mechanism-based inhibitor of CYP1A2. The clinical interaction between theophylline and antofloxacin was further validated by the in vitro results.
The results showed that antofloxacin increases the plasma theophylline concentration, partly by acting as a mechanism-based inhibitor of CYP1A2.
评估茶碱和安妥沙星在体内和体外的药代动力学相互作用。
12 名健康受试者参与了一项随机、5 天治疗和 3 向交叉设计的试验。受试者分别接受安妥沙星（第 1 天和第 2 天至第 5 天口服 400mg，第 1 天和第 5 天口服 200mg）、茶碱（每天两次口服 100mg，第 1 天和第 5 天早上剂量为 200mg）或茶碱加安妥沙星治疗。第 1 次和第 5 次给药后，对茶碱和安妥沙星的血药和尿药动力学进行了特征描述。还在人肝微粒体中研究了安妥沙星对茶碱代谢的影响。
5 天的安妥沙星治疗显著增加了茶碱的血药浓度-时间曲线下面积和峰血浆浓度，同时减少了茶碱代谢物的排泄。相反，茶碱对安妥沙星的药代动力学没有影响。使用人肝微粒体的体外研究表明，安妥沙星是 CYP1A2 的弱可逆和机制基础抑制剂。体外结果进一步验证了茶碱和安妥沙星之间的临床相互作用。
结果表明，安妥沙星增加了茶碱的血浆浓度，部分原因是作为 CYP1A2 的机制基础抑制剂。
