Banca de DEFESA: VALDEENE VIEIRA SANTOS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : VALDEENE VIEIRA SANTOS
DATA : 04/10/2019
HORA: 14:00
LOCAL: Sala 7 Faculdade de Farmácia
TÍTULO:

Evaluation of pharmacokinetics and renal penetration of amphotericin B in healthy and Candida albicans infected WISTAR rats using the technique of microdialysis

PALAVRAS-CHAVES:

Amphotericin B. C. albicans. Pharmacocokinetics. Microdialysis. Tissue penetration. 

PÁGINAS: 79
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

Systemic candidiasis is a common opportunistic fungal infection, especially in hospitalized and immunosuppressed patients. Candida albicans is the most common causative agent and most isolated species in these infections, and amphotericin B (AmB) is used for its treatment. For it to have the expected action, it must be able to access its site of action in sufficient concentrations and in its free form, and that the infected tissue does not influence tissue distribution. Therefore, the objectives of this study were to evaluate the pharmacokinetics and renal penetration of AmB by microdialysis (MD) in healthy Wistar rats infected with C. albicans. For this, an analytical and bioanalytical method for the quantification of AmB in microdialysis and plasma of rats was validated. The method was validated using High Performance Liquid Chromatography coupled with a diode array detector (HPLC/ DAD). The mobile phase consisted of acetate buffer (pH = 4) and gradient acetonitrile, effluent with a flow rate of 1.0 mL.min ^-1, and AmB detection was performed at 407 nm. Relative recovery of AmB by the MD probe was evaluated in vitro, with choice of perfusion flow and analysis of the influence of AmB concentration by the dialysis and retrodialysis method, and in vivo by retrodialysis. The pharmacokinetic and renal penetration study was performed after administration of 1 mg/kg (n = 10) and 2.5 mg/kg (n = 12) of AmB in healthy and C. albicans infected rats, blood and microdialysis samples at predetermined times. The quantification methods are selective and linear in the working range, with adequate precision and accuracy. The perfusion flowrate of the MD probes chosen was 1.5 μL/min, with a relative recovery of 22.5 ± 8.5% and 20.0 ± 6.0% for dialysis and retrodialysis, respectively. Relative recovery of the different concentrations did not show significant difference between dialysis and retrodialysis. Renal in vivo recovery was 10.9 ± 3.7%. After non-compartmental analysis of both plasmatic and renal concentrations and population modeling of plasma data obtained, it can be concluded that C. albicans infection was statistically significant for parameter Vd, and tissue penetration was different between groups (1.6 and 1.1, healthy and infected rats, respectively), with lower tissue distribution of AmB in the infected animals.

MEMBROS DA BANCA:
Presidente - 1012812 - FRANCINE JOHANSSON AZEREDO
Interno - 2055299 - ANA LEONOR PARDO CAMPOS GODOY
Externo à Instituição - SANDRA ELISA HAAS - Unipampa