Experimental models for pharmacokinetic and pharmacodynamic studies of antifungals in the cryptococcosis treatment

Cryptococcus spp. are basidiomycete fungi with a unique phenotypic peculiarity, the mucopolysaccharide capsule that circulate all the cell body. Cryptococcus spp. are broadly found in the environment, but there are two species are associated to disease in humans and other animals: Cryptococcus neoformans and Cryptococcus gattii complexes. Experimental studies on cryptococcosis in mammal animal model have demonstrated the occurrence of CNS infection and similarities in the fungal pathogenicity with clinical and immunological features of the human infection. There is still a lack of studies involving pharmacokinetics and pharmacodynamics (PK/PD) in animal models of cryptococcosis in the literature and these experimental models are useful to understand this mycosis and antifungal effectiveness for improving the therapeutic schemes. The scope of this review is to describe and discuss the main mammal animal models for PK/PD studies of antifungals used in the cryptococcosis treatment. Alternative models and computational methods are also addressed. Therefore, all approaches to PK/PD studies are relevant to investigate the drug-infection interaction and consequently to improve the cryptococcosis therapy.