Publications by authors named "Marina Rocha Galdino-Pitta"

2 Publications

  • Page 1 of 1

New Pioglitazone Metabolites and Absence of Opened-Ring Metabolites in New -Substituted Thiazolidinedione.

Drug Metab Dispos 2018 06 4;46(6):879-887. Epub 2018 Apr 4.

Department of Pharmacy, Universidade Federal do Paraná, Curitiba, Paraná, Brazil (M.L.C., L.B.C., R.P.); Department of Natural Active Principles and Toxicology, Faculdade de Ciências Farmacêuticas, São Paulo University (UNESP), Araraquara, São Paulo, Brazil (B.C.U.S., T.B.F., R.G.P.); and Laboratory of Design and Drug Synthesis, Universidade Federal de Pernambuco, Pernambuco, Brazil (M.R.G.-P., I.R.P.)

Thiazolidinediones (TZDs) are drugs used to treat type 2 diabetes mellitus; however, several safety concerns remain regarding the available drugs in this class. Therefore, the search for new TZD candidates is ongoing; metabolism studies play a crucial step in the development of new candidates. Pioglitazone, one of the most commonly used TZDs, and GQ-11, a new -substituted TZD, were investigated in terms of their metabolic activity in rat and human liver microsomes to assess their metabolic stability and investigate their metabolites. Methods for preparation of samples were based on liquid-liquid extraction and protein precipitation. Quantitation was performed using liquid chromatography (LC)-tandem mass spectrometry, and the metabolite investigation was performed using ultraperformance LC coupled to a hybrid quadrupole-time of flight mass spectrometer. The predicted intrinsic clearance of GQ-11 was 70.3 and 46.1 ml/kg per minute for rats and humans, respectively. The predicted intrinsic clearance of pioglitazone was 24.1 and 15.9 ml/kg per minute for rats and humans, respectively. The pioglitazone metabolite investigation revealed two unpublished metabolites (M-D and M-A). M-A is a hydration product and may be related to the mechanism of ring opening and the toxicity of pioglitazone. The metabolites of GQ-11 are products of oxidation; no ring-opening metabolite was observed for GQ-11. In conclusion, under the same experimental conditions, a ring-opening metabolite was observed only for pioglitazone. The resistance of GQ-11 to the ring opening is probably related to -substitution in the TZD ring.
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http://dx.doi.org/10.1124/dmd.117.079012DOI Listing
June 2018

Simvastatin inhibits cytokines in a dose response in patients with rheumatoid arthritis.

Inflamm Res 2014 Apr 14;63(4):309-15. Epub 2014 Jan 14.

Laboratório de Imunomodulação e Novas Abordagens Terapêuticas, Núcleo de Pesquisa em Inovação Terapêutica Suely Galdino, Recife, Brazil.

Objective And Design: To evaluate the effects of simvastatin in peripheral blood mononuclear cell (PBMC) cytokines profiles and correlate with the disease state of rheumatoid arthritis (RA) patients.

Methods: The PBMC from 22 RA patients were purified and stimulated or not stimulated with phorbol myristate acetate/ionomycin and were treated with simvastatin in different doses. Cytokine levels were quantified by ELISA and patients were assessed for clinical and laboratory variables. This assessment included disease activity measures [Clinical Disease Activity Index (CDAI), Disease Activity Score for 28 joints (DAS28)] and a Health Assessment Questionnaire.

Results: The IL-17A, IL-6, IL-22 and IFN-γ were significantly reduced in a dose response after simvastatin treatment (50 μM, p = 0.0005; p < 0.0001; p < 0.02; p = 0.0005, respectively). The IL-17A and IL-6 cytokines were also significantly reduced in lower concentrations of simvastatin (10 μM) compared to controls (p = 0.018; p = 0.04) and compared to the standard drug (p = 0.007; p = 0.0001). The results also showed that only RA patients with severe disease (DAS28 >5.1 and CDAI >22) had poor response to simvastatin in reducing cytokines levels, mainly for IL-17A and IL-22 cytokines (p = 0.03; p = 0.039, respectively).

Conclusion: The RA patients in clinical remission, mild or moderate had lower levels of all cytokines analyzed after simvastatin treatment, showing that these patients have better response to treatment. Our findings suggest that the simvastatin therapy modulates different cytokines in a dose dependent manner and its effect is associated with stratification of patients according to disease activity.
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http://dx.doi.org/10.1007/s00011-013-0702-4DOI Listing
April 2014
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