Pharmacokinetic interaction between itraconazole and ceftriaxone in Yucatan miniature pigs

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 (AUG) were 152.2 mu g . h/ml (standard deviation [SD], 22.5) and 129.2 mu g . 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,vith 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 itraconazoIe alone to 122.7 ng . h/ml with itraconazole and ceftriaxone combined in pig 1, from 398.5 to 315.7 ng . h/ml in pig 2, and from 979.6 to 716.6 ng . h/ml in pig 3 (P of <0.01 by analysis of variance).