Itraconazole-ciprofloxacin interaction on the pharmacokinetics of the intestinal compartment: preliminary results in rats
Abstract number: P1063
Benini A., Caveiari C., Franceschetti P., Bertazzoni E.
Among their pharmacokinetic characteristics fluoroquinolones (FQs) exhibit transintestinal and biliary elimination; moreover, they may interfere with hepatic metabolism. Interactions of FQs with enzymeinhibitors or inducers could be possible during therapy. The inhibitory effects on the hepatic metabolism of Itraconanzole (Itz) should be considered in the kinetics of FQs.
Objectives: To study the effect of Itz on intestinal kinetics of Ciprofloxacin (Cpx) following different administration schedule.
Methods: Wistar rats (weight 174.0+12.5 g, mean+SD) divided in three groups were treated as follows: group 1: Cpx, 15 mg/kg/day, orally administered by gavage for three days; group 2: Cpx two hours after oral administration of Itz (10 mg/kg/day) for three days; group 3: Cpx for 3 days and Itz (10 mg/kg/day) on the 2nd and 3rd day of Cpx administration. Samples of blood, intestinal and hepatic tissues and faeces were collected after three days of treatment, two hours after the last Cpx administration. Cpx concentrations were determined by microbiological assay (agar-well diffusion method, K. pneumoniae, Isosensistest agar).
Results: reported in the table as mean+SD
After three days of Itz administration the levels of Cpx increased significantly in liver and faeces (not significantly) while decreased in serum (1/4 positive samples) and intestinal tissues. The administration of Itz for 2 days in rats in treatment with Cpx induced a significant increase of Cpx serum levels, a reduction of intestinal levels and a marked decrease in faeces in comparison to Cpx alone.
Conclusions: These preliminary results suggest a possible involvement of Itz on the intestinal secretory mechanisms of Cpx and changes in the enterohepatic circulation. The inhibitory effects of Itz on the Cpx intestinal pharmacokinetics seems different according to timing of Itz administration.
MIUR PRIN 2003-Prot. N. 2003051858_003
|Session name:||18th European Congress of Clinical Microbiology and Infectious Diseases|
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