A New Model of Drug-Disease Interaction in Rabbits

摘要

Background： Drug-infection interaction should be considered in drug prescribing, particularly if potentiated byco-occuring drug-drug interactions. The effects of Candida and e-coli infections separately, and fluconazole administration weretested on cyclosporine blood level in rabbits. Methods： Three study designs were carried out, crossoversingle-dose-fluconazole-cyclosporine study testing fluconazole-cyclosporine interaction, multi-dosecandida-fluconazole-cyclosporine and multi-dose escherichia coli-cyclosporine study designs involving each rabbit acting as itscontrol; cyclosporine was given daily in both studies. Candida and e-coli infections were inoculated on day 5. In theMulti-Candida-Fluc-CyA, fluconazole-cyclosporine interaction was also considered, and flueonazole was administered daily fromday 9-18. In all three studies, Cyclosporine trough levels and serum creatinine were measured by CMIA and enzymatic assayrespectively, pre, during, post-infection and after fluconazole administration in the Candida study. Results： Both infections resulted insignificant rise in cyclosporine trough level （p = 0.018） and （p = 0.005） in fungal and bacterial studies, respectively. The median risein CyA level reached 52% （range 9-426%） in the Candida infection and reached 60 - 47.5% （mean） with the e-coli infection.Fluconazole also increased mean cyclosporine trough levels in the single-dose study by 70.3 - 45.3 and the concomitant rise inthemulti-dose study reached 76% （median, range 22-665%）. Conclusions： Cyclosporine trough levels increased during Candida ande-coli infections and also during fluconazole administration in the single and multi-dose studies. Fluconazole exerted an additiveeffect to the Candida inhibitory effect. Type of infection and inoculum size affected CyA levels differently. Monitoring cyclosporinelevel during episodes of infection as well as in therapy regimen involving interacting drugs is advisable.