Pharmacokinetic/Pharmacodynamic Modeling of Renin-Angiotensin Aldosterone Biomarkers Following Angiotensin-Converting Enzyme (ACE) Inhibition Therapy with Benazepril in Dogs.
Pharm Res
; 32(6): 1931-46, 2015 Jun.
Article
em En
| MEDLINE
| ID: mdl-25446774
ABSTRACT
PURPOSE:
The objective of this research was to provide a comprehensive description of the effect of benazepril on the dynamics of the renin-angiotensin aldosterone system (RAAS) in dogs.METHODS:
Blood specimens for renin activity (RA), angiotensin II (AII), and aldosterone (ALD) quantitation in plasma were drawn from 12 healthy adult beagle dogs randomly allocated to 2 treatment groups (i) benazepril 5 mg PO, q24 h (n 6) and (ii) placebo (n 6), in a cross-over design. A mechanism-based pharmacokinetic/pharmacodynamic model, which includes the periodic nature of RA, AII, and ALD during placebo treatment and the subsequent changes in dynamics following repeated dosing with benazepril, was developed.RESULTS:
The disposition kinetics of benazepril active metabolite, benazeprilat, was characterized using a saturable binding model to the angiotensin converting enzyme. The modulatory effect of benazeprilat on the RAAS was described using a combination of immediate response models. Our data show that benazepril noticeably influences the dynamics of the renin cascade, resulting in a substantial decrease in AII and ALD, while increasing RA throughout the observation span.CONCLUSIONS:
The model provides a quantitative framework for better understanding the effect of ACE inhibition on the dynamics of the systemic RAAS in dogs.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Sistema Renina-Angiotensina
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Benzazepinas
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Inibidores da Enzima Conversora de Angiotensina
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Modelos Biológicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article