Physiologically based pharmacokinetics of radioiodinated human beta-endorphin in rats. An application of the capillary membrane-limited model.
Drug Metab Dispos
; 15(4): 540-50, 1987.
Article
em En
| MEDLINE
| ID: mdl-2888629
ABSTRACT
In order to simulate the distribution and elimination of radioiodinated human beta-endorphin (125I-beta-EP) after iv bolus injection in rats, we proposed a physiologically based pharmacokinetic model incorporating diffusional transport of 125I-beta-EP across the capillary membrane. This model assumes that the distribution of 125I-beta-EP is restricted only within the blood and the tissue interstitial fluid, and that a diffusional barrier across the capillary membrane exists in each tissue except the liver. The tissue-to-blood partition coefficients were estimated from the ratios of the concentration in tissues to that in arterial plasma at the terminal (pseudoequilibrium) phase. The total body plasma clearance (9.0 ml/min/kg) was appropriately assigned to the liver and kidney. The transcapillary diffusion clearances of 125I-beta-EP were also estimated and shown to correlate linearly with that of inulin in several tissues. Numerically solving the mass-balance differential equations as to plasma and each tissue simultaneously, simulated concentration curves of 125I-beta-EP corresponded well with the observed data. It was suggested by the simulation that the initial rapid disappearance of 125I-beta-EP from plasma after iv injection could be attributed in part to the transcapillary diffusion of the peptide.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Beta-Endorfina
Limite:
Animals
Idioma:
En
Ano de publicação:
1987
Tipo de documento:
Article