Physiologically based pharmacokinetics of radioiodinated human beta-endorphin in rats. An application of the capillary membrane-limited model.
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.
D000818:Animals; D002196:Capillaries / Q000378:metabolism; D002850:Chromatography, Gel; D004058:Diffusion; D006207:Half-Life; D007457:Iodine Radioisotopes; D008297:Male; D008657:Metabolic Clearance Rate; D008954:Models, Biological; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution; D001615:beta-Endorphin / Q000302:isolation & purification / Q000493:pharmacokinetics*
D007457:Iodine Radioisotopes; D001615:beta-Endorphin