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Selection of the candidate compound at an early stage of new drug development: retrospective pharmacokinetic and metabolic evaluations of valsartan using common marmosets.
Matsumoto, Shogo; Uehara, Shotaro; Kamimura, Hidetaka; Cho, Naoki; Ikeda, Hiroshi; Maeda, Satoshi; Kagiyama, Kensuke; Miyata, Atsunori; Suemizu, Hiroshi; Fukasawa, Kazumasa.
Afiliación
  • Matsumoto S; Drug and Discovery and Management Department, R and D Division, Meiji Seika Pharma Co., Ltd, Tokyo, Japan.
  • Uehara S; Department of Applied Research for Laboratory Animals, Central Institute for Experimental Animals, Kawasaki, Japan.
  • Kamimura H; Department of Applied Research for Laboratory Animals, Central Institute for Experimental Animals, Kawasaki, Japan.
  • Cho N; Business Promotion Department, CLEA Japan, Inc, Tokyo, Japan.
  • Ikeda H; Drug and Discovery and Management Department, R and D Division, Meiji Seika Pharma Co., Ltd, Tokyo, Japan.
  • Maeda S; Tokyo Animal and Diet Department, CLEA Japan, Inc, Tokyo, Japan.
  • Kagiyama K; Yaotsu Breeding Center, CLEA Japan, Inc, Gifu, Japan.
  • Miyata A; Yaotsu Breeding Center, CLEA Japan, Inc, Gifu, Japan.
  • Suemizu H; Drug and Discovery and Management Department, R and D Division, Meiji Seika Pharma Co., Ltd, Tokyo, Japan.
  • Fukasawa K; Department of Applied Research for Laboratory Animals, Central Institute for Experimental Animals, Kawasaki, Japan.
Xenobiotica ; 52(6): 613-624, 2022 Jun.
Article en En | MEDLINE | ID: mdl-36148579
Valsartan is an antihypertensive drug that was developed using common marmosets (Callithrix jacchus) in pivotal toxicity studies as a non-rodent species. The aim of the present study was to investigate the utility of marmosets in the candidate selection of this drug from a pharmacokinetic and metabolic viewpoint.Valsartan, as well as three other angiotensin II type-I receptor blockers, assumed as competitive candidates, were administered to common marmosets. Human pharmacokinetic parameters predicted by single-species allometric scaling and Wajima superposition suggested that valsartan may exhibit promising pharmacokinetic properties in humans.In vitro metabolic studies of valsartan using isolated rat, dog, marmoset, cynomolgus monkey, and human hepatocytes revealed that the marmoset was the most relevant animal species to humans presenting with the most abundant human metabolite, 4-hydroxyvalsartan. Oral administration of an elevated dose of valsartan to a common marmoset demonstrated that the level of 4-hydroxyvalsartan in the plasma was comparable to that in clinical practice and suggested that safety of the human metabolite might have been confirmed in the toxicity studies using common marmosets.These results suggest that common marmosets, the small, non-human primates, had been a suitable species for the development of valsartan.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Callithrix / Antihipertensivos Tipo de estudio: Observational_studies Límite: Animals / Humans Idioma: En Revista: Xenobiotica Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Callithrix / Antihipertensivos Tipo de estudio: Observational_studies Límite: Animals / Humans Idioma: En Revista: Xenobiotica Año: 2022 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido