Journal of Pharmaceutical Care & Health Systems
Open Access
ISSN: 2376-0419
+44 1300 500008
ISSN: 2376-0419
+44 1300 500008
Padilha E C1, Campos M L1, De Grandis R1, Varanda E A1, Pitta I R2 and Peccinini R G1
1Sao Paulo State University, Brazil 2Federal University of Pernambuco, Brazil
Posters-Accepted Abstracts: J Pharma Care Health Sys
Thiazolidinediones (TZDs) are PPAR-�³ (Peroxisome Proliferator Activated Receptors) activating drugs. Although this target has been previously studied for diabetes treatment, it has also been proven useful in atherosclerosis treatment which led the Researchers of the Laboratory of Planning and Synthesis of Drugs at the Federal University of Pernambuco to select several TZD derivatives with promising anti-atherosclerosis activity. Among the compounds with best performances that emerged were GQ-2, GQ-11, GQ-19 and GQ-177. These drug candidates were submitted to a screening in order to determine which of these compounds would have desirable intestinal permeability. Thus, we performed a Caco-2 permeability assay and determined that the physicochemical characteristics often related to the permeability a drug, logP. Caco-2 cells showed trans-epithelial electrical resistance (TEER) >300 �©/cm�² and were fit for the experiment. Benznidazol was used as positive control and amphotericin B as negative control. The logP was determined through the chromatographic method established by OECD. In the results, the logP values were ~6.41, 5.11, 1.87 and 3.5 for GQ-2, GQ-11, GQ-19 and GQ-177, respectively. The only compound that showed any Caco-2 permeability was GQ-19, the substance with the lowest logP, with apparent permeability (Papp) of 1.58 x10-5(�±6.06x10-7) cm/s, while benznidazol have shown Papp of 2.86 x10-5(�± 2.87x10-6) cm/s. These results endorse a refined study on the oral activity of GQ-19 which is the only molecule of the batch to integrally permeate a human monolayer of cells and act as predicted.
Padilha E C is has a master’s degree in Toxicology from Sao Paulo State University. He is currently a PhD student in Pharmacology with emphasis in Pharmacokinetics. He is a researcher in preclinical pharmacokinetics and toxicology of new molecules and formulations and has published 6 papers in reputed journal of pharmacokinetics, toxicology, drug discovery, biopharmaceutics and chromatography.
Email: eliascarvalho@gmail.com