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Comparative physiology of mice and rats: radiometric measurement of vascular parameters in rodent tissues.
Boswell, C Andrew; Mundo, Eduardo E; Ulufatu, Sheila; Bumbaca, Daniela; Cahaya, Hendry S; Majidy, Nicholas; Van Hoy, Marjie; Schweiger, Michelle G; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A.
Afiliação
  • Boswell CA; Genentech Research and Early Development , South San Francisco 94080, United States.
Mol Pharm ; 11(5): 1591-8, 2014 May 05.
Article em En | MEDLINE | ID: mdl-24702191
ABSTRACT
A solid understanding of physiology is beneficial in optimizing drug delivery and in the development of clinically predictive models of drug disposition kinetics. Although an abundance of data exists in the literature, it is often confounded by the use of various experimental methods and a lack of consensus in values from different sources. To help address this deficiency, we sought to directly compare three important vascular parameters at the tissue level using the same experimental approach in both mice and rats. Interstitial volume, vascular volume, and blood flow were radiometrically measured in selected harvested tissues of both species by extracellular marker infusion, red blood cell labeling, and rubidium chloride bolus distribution, respectively. The latter two parameters were further compared by whole-body autoradiographic imaging. An overall good interspecies agreement was observed for interstitial volume and blood flow on a weight-normalized basis in most tissues. In contrast, the measured vascular volumes of most rat tissues were higher than for mouse. Mice and rats, the two most commonly utilized rodent species in translational drug development, should not be considered as interchangeable in terms of vascular volume per gram of tissue. This will be particularly critical in biodistribution studies of drugs, as the amount of drug in the residual blood of tissues is often not negligible, especially for biologic drugs (e.g., antibodies) having long circulation half-lives. Physiologically based models of drug pharmacokinetics and/or pharmacodynamics also rely on accurate knowledge of biological parameters in tissues. For tissue parameters with poor interspecies agreement, the significance and possible drivers are discussed.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ratos / Volume Sanguíneo / Camundongos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Pharm Assunto da revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ratos / Volume Sanguíneo / Camundongos Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Mol Pharm Assunto da revista: BIOLOGIA MOLECULAR / FARMACIA / FARMACOLOGIA Ano de publicação: 2014 Tipo de documento: Article País de afiliação: Estados Unidos