Pharmacokinetic/pharmacodynamic modeling of antipyretic and anti-inflammatory effects of naproxen in the rat.
J Pharmacol Exp Ther
; 297(1): 198-205, 2001 Apr.
Article
em En
| MEDLINE
| ID: mdl-11259545
ABSTRACT
Pharmacokinetic/pharmacodynamic modeling was used to characterize the antipyretic and anti-inflammatory effects of naproxen in rats. An indirect response model was used to describe the antipyretic effects of naproxen after short intravenous infusions. The model assumes that basal temperature (T(a)) is maintained by the balance of fever mediators given by a constant (zero order) rate of synthesis (K(syn)), and a first order rate of degradation (K(out)). After an intraperitoneal injection of lipopolysaccharide, the change in T(a) was modeled assuming an increase in fever mediators described as an input rate function [IR(t)] estimated nonparametrically. An inhibitory E(max) model adequately described the inhibition of IR(t) by naproxen. A more complex model was used to describe the anti-inflammatory response of oral naproxen in the carrageenin-induced edema model. Before carrageenin injection, physiological conditions are maintained by a balance of inflammation mediators given by K(syn) and K(out) (see above). After carrageenin injection, the additional synthesis of mediators is described by IR(t) (see above). Such mediators induced an inflammatory process, which is governed by a first order rate constant (K(IN)) that can be inhibited by the presence of naproxen in plasma. The sigmoidal E(max) model also well described the inhibition of K(IN) by naproxen. Estimates for IC(50) [concentration of naproxen in plasma eliciting half of maximum inhibition of IR(t) or K(IN)] were 4.24 and 4.13 microg/ml, for the antipyretic and anti-inflammatory effects, respectively.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Anti-Inflamatórios não Esteroides
/
Naproxeno
/
Analgésicos não Narcóticos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharmacol Exp Ther
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Espanha