PHARMACOKINETIC INTERACTION BETWEEN ITRACONAZOLE AND CEFTRIAXONE IN YUCATAN MINIATURE PIGS

Since ceftriaxone and itraconazole are highly protein bound, are excre ted via a biliary pathway, and are in vitro modulators of the efflux p ump P glycoprotein, a pharmacokinetic interaction between these antimi crobial agents can be hypothesized. Therefore, we evaluated the pharma cokinetics 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 conc entration-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-liv es 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 itracon azole kinetics, ceftriaxone was shown to alter the disposition of the triazole. Contrary to what was expected, the AUC (from 0 to 8 h) decre ased from 139.3 ng . h/ml with itraconazoIe alone to 122.7 ng . h/ml w ith 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).