After the oral government, the absorption of the drug depends on the dose regimen and the amount of fat in the food

After the oral government, the absorption of the drug depends on the dose regimen and the amount of fat in the food. pharmacology of voriconazole and posaconazole as well as to explain the indications and contraindications of using the drugs, determine factors influencing their pharmacotherapy, and provide information that might be helpful in the treatment of fungal infections. Keywords: voriconazole, posaconazole, clinical pharmacology, cytochrome P-450 enzyme system, drug monitoring == Launch == Fungal infections are one of the most severe problems in clinical practice, especially in hematology and oncology units. They make up coming from 9 to 10% of all infections developing among hospitalized patients. Fungemia can be either a complication connected DIAPH2 with the malignancy itself or an adverse effect of the oncological treatment (chemo-, radio- and corticotherapy). Furthermore, it can influence the final result of treatment. In the group of individuals with oncological diseases, allogenic bone marrow 3,3′-Diindolylmethane transplantations, relapse of leukemia, pancytopenia enduring longer than ten days, undergoing corticotherapy and broad-spectrum antibiotic therapy, immunosuppressive treatment and graft versus web host disease (GVHD) are the main factors predisposing to fungal infections. Pathogens mainly responsible for invasive 3,3′-Diindolylmethane fungal infections (IFI) areCandidaspp. andAspergillusspp. The 1st kind frequently develops as a concurrent disease during acute mucosa inflammation, infections connected with central venous catheters and the use of broad-spectrum antibiotics, and pre-existing colonization with the pathogen in at least 1 body area. The second kind leads to contamination resulting from inhalation of spores from the air flow. This is why pulmonary aspergillosis is one of the most frequent infections caused byAspergillusspp. (87% of patients), followed by sinusitis and rhinitis (16%), and less frequently encephalitis (8%). The risk factors of aspergillosis are neutropenia lasting for longer than two weeks, staying in an endemic region, tuberculosis and cytomegalic disease infection. The danger factors promoting fungal infections are presented inTable 1[18]. == Table 1 . == Risk factors promoting fungal infections The rate of recurrence of fungal infections is still growing, and the prophylactic and empiric antifungal treatment using extended spectrum drugs leads to development of resistance. Unfortunately, such infections are not easy to diagnose, especially in their early stages. This is primarily connected with their nonspecific character similar to disease and bacterial infections, affecting immunocompromised patients, few symptoms usually limited to pyrexia, decreased options of diagnostic screening in individuals in a serious condition, and false bad results of performed diagnostic tests. It has been determined the median mortality rate among patients, after chemotherapy, caused by invasive yeast infections is 39% and it varies among different types of fungi. As an example, the mortality price inAspergillusspp. infections is 49. 3% and it can rise to 86. 7% in individuals after hematopoietic cell transplantation. For individuals with candidiasis the 3,3′-Diindolylmethane mortality rate is about 1436%, to get invasive fusariosis it is much higher, and varies from 66 to 75%, and for scedosporiosis the estimated mortality rate is usually between 65 and totally [911]. Every individual with neutropenia and long-lasting pyrexia that is not getting better after antibiotic therapy should be suspected of fungal infection, and there is an urgent need to carry out laboratory assessments. Diagnostic methods covering microscopic, microbiologic, serologic and genetic testing help to decide which pharmacological treatment would be the best [2, three or more, 12]. For over 40 years, the treatment of fungal infections was based on amphotericin W. The numerous adverse effects, especially nephrotoxicity, forced scientists to search for other drugs. In the 1980s, a new generation azole antifungal drugs entered therapeutic use. With respect to the amount of nitrogen atoms in the azole ring, the new pharmacotherapeutic group has been divided into imidazoles (with 2 nitrogen atoms) displayed by ketoconazole, miconazole, clotrimazole, tioconazole, econazole, isoconazole, and triazoles (3 nitrogen atoms) the 1st generation with fluconazole and itraconazole, the second generation with voriconazole and posaconazole [13, 14]. The goal of this article is to present and compare the clinical pharmacology of the new generation triazole drugs voriconazole (approved to get therapy in 2002) and posaconazole (approved for therapy in 2006) [13]. == Mode of action and therapeutic indications == The mode of action of voriconazole and posaconazole is the inhibition of fungal cytochrome P450 mediated 14-alpha lanosterol demethylation, which causes damage in the structure and the lack of cell membrane function. Voriconazole is a broad spectrum antifungal agent indicated for the treatment of candidiasis also caused by fluconazole-resistantC. glabrataandC. krusei. Moreover, it can be used inAspergillus(A. flavus, A. fumigatus, A. terreus, A. niger, A. nidulans), Cryptococcus neoformans, Fusarium, Scedosporium, Penicillium, Alternaria, Blastomyces.