Pharmacokinetics of hydroxymethylnitrofurazone and its parent drug nitrofurazone in rabbits

The prodrug hydroximethylnitrofurazone (NFOH) presents antichagasic activity with greatly reduced toxicity compared to its drug matrix nitrofurazone (NF). Besides these new characteristics, the prodrug was more active against the parasite T. cruzi amastigotes. These advantages make the prodrug a possible therapeutic alternative for the treatment of both acute and the chronic phase of Chagas disease. However, the knowledge of pharmacokinetic profile is crucial to evaluate the feasibility of a new drug. In this study, our objective was to evaluate the in vivo formation of NF from the NFOH single administration and to evaluate its pharmacokinetic profile and compared it to NF administration. A bioanalytical method to determine the NF and NFOH by LCMS/MS was developed and validated to perform these investigations. Male albino rabbits (n=15) received NF intravenously and orally in doses of 6.35 and 63.5 mg / kg respectively, and NFOH, 80.5 mg / kg orally. The serial blood samples were processed and analyzed by mass spectrometry. The system operated in positive and negative modes for the analites determination, under elution of the mobile phase 50:50 water: methanol. The administration of NFOH allowed the calculation of pharmacokinetic parameters for the prodrug, and the NF obtained from NFOH administration. Using the pharmacokinetic profile obtained from the NF i.v. administration, the oral bioavailability of NF from the administered prodrug was obtained (60.1%) and, as a key parameter in a prodrug administration, should be considered in future studies. The i.v. and oral administrations of NF differ in the constant of elimination (0.04 vs 0.002) and elimination half-life (17.32 min vs 276.09 min) due to the low solubility of the drug that hinders the formation of molecular dispersions in the digestory tract. Still, there was observed no statistical differences were observed between the pharmacokinetic parameters of orally administered NF and NF obtained from NFOH. The calculated area under the curve (AUC 0-∞) showed that the exposure to the parental drug was fairly the same (844.79 vs 566.44) for NF and NF obtained from the prodrug administration. The tendency to higher NF's mean residence time (MRT) as observed in the prodrug administration (956.1 min vs 496.3 min) guarantees longer time for the action of the drug and it allows the expansion of the administration intervals. These findings, added with the beneficial characteristics of the prodrug encourage new efficacy tests towards the clinical use of NFOH.

First detection of Leishmania spp. DNA in Brazilian bats captured strictly in urban areas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Caracterização morfológica, perfil químico, atividade biológica e conservação in situ do gênero Lychnophora Mart. (Asteraceae: Vernonieae: Lychnophorinae), Brasil

Many people who live in the cerrado regions use plant species for therapeutic purposes. However, due to intensive extraction of some species, native botanical populations are at risk of disappearing or suffering a dramatic decrease, such as, for instance, individuals of the Lychnophora genus. This has 24 species distributed into the categories vulnerable, endangered, critically endangered, and possibly extinct. These individuals are known in folk medicine as “arnica” and their leaves and flowers are commonly used as anti-inflammatory, analgesic, and healing agents. The chemical profile of the genus is characterized by the presence of sesquiterpene lactones, sesquiterpenes, diterpenes, triterpenes, flavonoids, steroids, polyacetylenes, and caryophyllene derivatives which also have lignans with analgesic activity. Studies with Lychnophora species show significant results with regard to their biological activities against Leishmania amazonensis, Staphylococcus aureus, and Tripanosoma cruzi. Therefore, this study aimed to perform a survey of the morphology, chemical composition, and biological activity, as well as the use and current conservation status of the Lychnophora genus in Brazil.