Does Cryptococcus neoformans infection alter antifungal distribution: an animal model exploring pharmacokinetic changes

Assessing the disseminated meningitis caused by Cryptoccocus neoformans in Wistar rats and its impact on antifungal distribution by microdialysis (µD). The yeast presence was investigated in different tissues by histological and microbiological assays, and biochemical parameters such as urea, glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatinine, creatine kinase (CK), creatinine, albumin level, leukocyte counts, and brain vascular permeability (Evans blue test) were evaluated in healthy and infected groups. Levels of fluconazole reached in the animal's brain were determined by µD. Differences in albumin, urea, GPT, and CK between healthy and infected animals were observed in the levels of Evans blue as well as in the brain (0.51 vs 1.50 µg/gbrain). The drugs' distribution in the brain of infected animals was higher than that in the brain of healthy ones (ft = 1.37 vs ft = 0.54). The model validated presents characteristics similar to those observed in patients and can be applied to pharmacokinetic investigations.