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Master's Dissertation
DOI
10.11606/D.5.2006.tde-24052006-163909
Document
Author
Full name
Maria Luiza Nogueira Dias Genta
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2006
Supervisor
Committee
Carvalho, Jesus Paula (President)
Maranhao, Raul Cavalcante
Schivartche, Paulo Levy
Title in Portuguese
"Farmacocinética e captação tecidual do paclitaxel associado à nanoemulsão (LDE) em pacientes com neoplasias malignas do trato genital feminino"
Keywords in Portuguese
Emulsões
Lipoproteínas LDL
Neoplasias do colo uterino
Neoplasias do endométrio
Neoplasias ovarianas
Paclitaxel
Quimioterapia
Sistemas de liberação de medicamentos
Abstract in Portuguese
O paclitaxel é utilizado amplamente no carcinoma de ovário, nos casos refratários de carcinoma de endométrio e quimioterapia exclusiva para carcinoma avançado de colo uterino. A associação de paclitaxel a uma nanoemulsião rica em colesterol, denominada LDE, mostrou toxicidade menor e aumento da atividade antitumoral do fármaco em cobaias. No presente estudo, investigou-se os parâmetros farmacocinéticos do oleato de LDE-paclitaxel e a habilidade da LDE de concentrar o fármaco no tumor em oito pacientes com câncer do trato genital feminino. O oleate de paclitaxel associado a LDE é estável na circulação e tem uma meia-vida plasmática maior do que o paclitaxel comercial. A LDE concentra 3,6 mais paclitaxel em tecidos tumorais do que nos tecidos normais. Esta associação parece ser uma alternativa no tratamento dos tumores ginecológicos
Title in English
Pharmacokinetics and tumor uptake of a derivatized form of paclitaxel associated to a cholesterol-rich nanoemulsion (LDE) in patients with gynecologic cancers
Keywords in English
Cervix neoplasms
Drug delivery systems
Drug therapy
Emulsions
Endometrial neoplasms
Lipoproteins LDL
Ovarian neoplasms
Paclitaxel
Abstract in English
A cholesterol-rich nanoemulsion termed LDE concentrates in cancer tissues after injection into the bloodstream. The association of a derivatized paclitaxel to LDE showed lower toxicity and increased antitumoral activity as tested in mice. Here, the pharmacokinetics of LDE-paclitaxel oleate and the ability of LDE to concentrate the drug in the tumor were investigated in eight patients with gynecologic cancers. Fractional clearance rate (FCR) and pharmacokinetic parameters were calculated by compartmental analysis. Also, specimens of tumors and the normal tissues were excised during the surgery for radioactivity measurement. LDE concentrates 3.5 more paclitaxel in malignant tissues than in the normal tissues. Therefore, association to LDE is an interesting strategy for using paclitaxel to treat gynecologic cancers
 
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Publishing Date
2006-05-26
 
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