Cavalier A, Levêque D, Peter J D, Salmon J, Elkhaïli H, Salmon Y, Nobelis P, Geisert J, Monteil H, Jehl F
Laboratoire de Pharmacocinétique de l'Institut de Bactériologie, Strasbourg, France.
Antimicrob Agents Chemother. 1997 Sep;41(9):2029-32. doi: 10.1128/AAC.41.9.2029.
Since ceftriaxone and itraconazole are highly protein bound, are excreted via a biliary pathway, and are in vitro modulators of the efflux pump P glycoprotein, a pharmacokinetic interaction between these antimicrobial agents can be hypothesized. Therefore, we evaluated the pharmacokinetics of itraconazole and ceftriaxone alone and in combination in a chronic model of catheterized miniature pigs. Itraconazole does not influence ceftriaxone kinetic behavior. The mean areas under the concentration-time curve (AUC) were 152.2 microg x h/ml (standard deviation [SD], 22.5) and 129.2 microg x h/ml (SD, 41.2) and the terminal half-lives were 1.1 h (SD, 0.3) and 0.9 h (SD, 0.2) when ceftriaxone was given alone and combined with itraconazole, respectively. Regarding itraconazole kinetics, ceftriaxone was shown to alter the disposition of the triazole. Contrary to what was expected, the AUC (from 0 to 8 h) decreased from 139.3 ng h/ml with itraconazole alone to 122.7 ng h/ml with itraconazole and ceftriaxone combined in pig 1, from 398.5 to 315.7 ng x h/ml in pig 2, and from 979.6 to 716.6 ng x h/ml in pig 3 (P of <0.01 by analysis of variance).
由于头孢曲松和伊曲康唑与蛋白质高度结合，通过胆汁途径排泄，并且是外排泵P糖蛋白的体外调节剂，因此可以推测这些抗菌药物之间存在药代动力学相互作用。因此，我们在导管插入微型猪的慢性模型中评估了伊曲康唑和头孢曲松单独使用及联合使用时的药代动力学。伊曲康唑不影响头孢曲松的动力学行为。单独给予头孢曲松和与伊曲康唑联合使用时，浓度-时间曲线下的平均面积（AUC）分别为152.2微克·小时/毫升（标准差[SD]，22.5）和129.2微克·小时/毫升（SD，41.2），终末半衰期分别为1.1小时（SD，0.3）和0.9小时（SD，0.2）。关于伊曲康唑的动力学，头孢曲松被证明会改变三唑的处置。与预期相反，在猪1中，AUC（从0至8小时）从单独使用伊曲康唑时的139.3纳克·小时/毫升降至伊曲康唑与头孢曲松联合使用时的122.7纳克·小时/毫升，在猪2中从398.5降至315.7纳克·小时/毫升，在猪3中从979.6降至716.6纳克·小时/毫升（方差分析P<0.01）。
