Sickle cell disease is the most common monogenic disorder and severe throughout the world. It is characterized by acute illness and progressive organ damage. Results from a single mutation at position 6 of ² chain, with glutamate in hemoglobin to valine in hemoglobin S. Aiming to treat the symptoms of this disease, the phtalimide derivative LAPDESF-SCD03 was planned to have nitric oxide donor activity and anti-inflammatory activity, which has been demonstrated in published studies. Through this, it is proposed this project to perform preclinical pharmacokinetic evaluation, pharmacokinetic/pharmacodynamic relationship and preliminary evaluation of hepatic and renal safety. Will be developed and validated analytical and bioanalytical method for drug quantification in the proposed studies. The pharmacokinetics will be assessed in Wistar rats by oral and intravenous administration. This assay allows the calculation of pharmacokinetic parameters, including oral bioavailability. These pharmacokinetic parameters are important for calculating dosage regimens in further studies to meet the motion of the drug in the body. The test will determine pharmacodynamic action of the drug in vivo and its relation to plasma concentrations observed. Already the preliminary test designed to assess safety if drugs lead to liver or kidney changes that undermine the continuity of its development, which merit more detailed assessment immediately or allow them to continue their studies with these new molecules. All these tests are important information in preclinical development of new drug, which will be part of the justifications at the time of a clinical research protocol.
News published in Agência FAPESP Newsletter about the scholarship: