Validação de método bioanalítico para avaliação da influência da ivermectina e ciclofosfomida na farmacocinética (pk) da carboplatina: ensaio pré-clínico

The use of different forms of chemotherapy is a therapeutic potential of anti-neoplastic drugs, in order to obtain maximum protocol efficiency and reduce adverse consequences. The objective is to validate the carboplatin analysis method in rat plasma and to evaluate the influence of cyclophosphamide on the pharmacokinetics of carboplatin in healthy rats (preclinical pilot test). We studied 24 Wistars rats, divided into three experimental groups: G1 - animals treated with carboplatin alone (n = 8), G2 - animals treated with carboplatin preceded by application of ivermectin and G3 - animals treated with carboplatin combined with a metronomic cyclophosphamide (n = 8). Blood was collected from all animals at times 0, 5, 15, 30, 45, 60, 120 and 240 minutes after carboplatin administration. After being harvested as rats, they were euthanized, sent to the Pathology Sector and submitted to necropsy. Fragments of kidneys, intestine, liver and lung were collected. As blood samples were centrifuged to obtain plasma for analysis of pharmacokinetics under the CLAE-UV (high performance liquid chromatography) method. The analytical method was linear, robust and reproducible, presenting validation in cadavers and partial in rats, being this a pilot study to evaluate the pharmacokinetics in female dog with mammary carcinomas. The dose of 50 mg / kg intravenously and on a single dose regimen is not altered. However, a trend in life and part increase in the cyclophosphamide group was observed when it was in the pilot group (carboplatin), which can also be seen in the reduction of drug clearance in the group. A common and discrete histopathological analysis of the circulatory and degenerative functions not renal and hepatic parenchyma of the treated rats. Thus, the association of carboplatin with an ivermectin is safe, synergistic and a dose can be performed without risk to the patient. However, in the association of carboplatin with cyclophosphamide, it is suggested to reduce the dose of carboplatin, seeking to potentiate the efficacy of its reactions by cyclophosphamide.

Grantor dc:publisher

Universidade Federal da Bahia

Year dc:date.issued

2019

Author dc:creator

• Silva, Laís Pereira

• Câncer de mama
• Biodisponibilidade
• Fármacos

Statement dc:rights

• Acesso Aberto

Language dc:language

por

Repository record dc:identifier.uri

https://repositorio.ufba.br/handle/ri/40409

OAI identifier oai:identifier

oai:repositorio.ufba.br:ri/40409