Biodistribution and Pharmacokinetics of Amblyomin-X, a Novel Antitumour Protein Drug in Healthy Mice

Autor(es)

Boufleur, Pamela ^[1] ; Sciani, Juliana Mozer ^{[1, 2]} ; Goldfeder, Mauricio ^[1] ; Faria, Fernanda ^[1] ; Branco, Vania ^[1] ; Chudzinski-Tavassi, Ana Marisa ^[1]

Afiliação do(s) autor(es)

^[1] Butantan Inst, Lab Mol Biol, Sao Paulo, SP - Brazil

^[2] Univ Sao Francisco, Lab Multidisciplinar Pesquisa, Av Francisco de Assis, 218 Cidade Univ, BR-12916900 Braganca Paulista, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS; v. 44, n. 1, p. 111-120, FEB 2019.
• Citações Web of Science: 2

Resumo

BackgroundAmblyomin-X is a recombinant protein under development for cancer treatment owing to its selective cytotoxic activity over several tumour cell lines and tumour regression in mice models. The aim of this study was to examine the distribution and pharmacokinetics of amblyomin-X in healthy female mice.MethodsAmblyomin-X was injected intravenously into the healthy animals and at controlled times plasma and organs were removed and analysed for identification and quantification of the protein. Alternatively, the labelled protein was injected into mice and tracked in an in vivo imaging system.ResultsAmblyomin-X was rapidly eliminated from plasma, probably because of its inability to bind to plasma albumin. After 10min, the protein was found in the thymus and lungs, and later in the heart, liver and kidneys. In the liver, the protein was found until 24h after a single injection. The in vivo analysis showed the same kinetics profile, besides the identification of amblyomin-X in the bladder region, indicating its elimination via urine. Only fragments of amblyomin-X were observed in the urine.ConclusionsThese findings suggest that amblyomin-X is rapidly distributed to the tissues, metabolized by the liver or even kidneys, and eliminated in urine in healthy mice. There is no accumulation in any organ. (AU)

• Processo FAPESP: 13/07467-1 - CeTICS - Centro de Toxinas, Imuno-Resposta e Sinalização Celular
• Beneficiário: Hugo Aguirre Armelin
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs