Banca de QUALIFICAÇÃO: MIGUEL ADELINO DA SILVA FILHO

Uma banca de QUALIFICAÇÃO de DOUTORADO foi cadastrada pelo programa.
DISCENTE : MIGUEL ADELINO DA SILVA FILHO
DATA : 06/02/2017
HORA: 10:00
LOCAL: Sala de Aula do PPGCSa
TÍTULO:

Semimechanistic model of amphotercin b and superaggregate forms against Candida albicans atcc

PALAVRAS-CHAVES:

Semimechanistic model; pkpd modeling; Amphotericin B and Heated amphotericin B

PÁGINAS: 25
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
RESUMO:

The Amphotericin B (AmB) still remains as a treatment choice of invasive fungal infections. However, the micellar form (AmB-D) presents serious adverse effects. The liposomal forms have low toxicity but they are costly. The heated AmB (AmB-H) can be an attempt to improve the AmB therapeutic index. The PDPD indexes are widely used however it presents some limitations. The PKPD modeling is a stepwise well accepted technique in drug development process. The aim of this work was to build a time-kill curve pharmacodynamic model of the AmB-D and AmB-H against ATCC Candida Albicans to support clinical decisions of AmB and also to check differences to AmB-H regarding the mechanism of action to support a drug development of AmB-H. The E_max model with two populations (susceptible and persistent) was the best description of the time-kill assay. Both formulations showed pharmacodynamic parameters quite similar nevertheless AmB-H showed a slight improvement. The E_max and EC50 of AmB-D was a bit higher than AmB-H. Therefore, at low concentrations, the slope (E_max/EC₅₀) is 8.267 L/mgh and 8.817 L/mgh for AmB-D and AmB-H, respectively. It indicates a slight high potency to AmB-H. Regarding to the resisting induction K_sp by AmB-D and AmB-H it was estimated at 1.55x10^-2 h^-1 and at 1.45x10^-2 h^-1, respectively. It indicates less drug resistance induction by AmB-H. The drug mechanism of action is mainly by AmB monomers doing membrane channels formations and by aggregate ones inducing peroxidation process on the fungal membrane. As AmB-H aggregates isn’t able to induce the peroxidation process which make this form less toxic to mammalian cells, we can infer the monomers forms has an important role in the pharmacodynamic mechanism and the normal aggregates can’t enhance the AmB activity as much. As the therapy costs keep increasing, AmB-H can be an affordable therapy choice for the future.

MEMBROS DA BANCA:
Interno - 1048067 - ANTONIO MANUEL GOUVEIA DE OLIVEIRA
Presidente - 1178187 - ERYVALDO SOCRATES TABOSA DO EGITO
Externo à Instituição - FRANCINE JOHANSSON AZEREDO - UFBA
Externo ao Programa - 2432313 - RAND RANDALL MARTINS