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Titolo:
The multiple indicator dilution method and its utility in risk assessment
Autore:
Schwab, AJ; Pang, KS;
Indirizzi:
McGill Univ, Montreal Gen Hosp, Med Clin, Montreal, PQ H3G 1A4, Canada McGill Univ Montreal PQ Canada H3G 1A4 Clin, Montreal, PQ H3G 1A4, Canada Univ Toronto, Dept Pharmacol, Toronto, ON, Canada Univ Toronto Toronto ONCanada onto, Dept Pharmacol, Toronto, ON, Canada Univ Toronto, Dept Pharmaceut Sci, Toronto, ON, Canada Univ Toronto Toronto ON Canada Dept Pharmaceut Sci, Toronto, ON, Canada
Titolo Testata:
ENVIRONMENTAL HEALTH PERSPECTIVES
, volume: 108, anno: 2000, supplemento:, 5
pagine: 861 - 872
SICI:
0091-6765(200010)108:<861:TMIDMA>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
PERFUSED-RAT-LIVER; HEPATIC-CLEARANCE MODELS; FORMATION IN-VIVO; DISPERSION MODEL; PHARMACOKINETIC MODEL; PARTITION-COEFFICIENTS; INTACT LIVER; BROMOSULFOPHTHALEIN-GLUTATHIONE; PHYSIOLOGICAL PHARMACOKINETICS; METABOLITE FORMATION;
Keywords:
capillary permeability; liver; metabolism; multiple indicator dilution method; partial differential equations; physiologically based pharmacokinetic models; quasi-steady-state approximation; risk assessment; time-invariant linear systems; transport;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Agriculture,Biology & Environmental Sciences
Life Sciences
Citazioni:
115
Recensione:
Indirizzi per estratti:
Indirizzo: Schwab, AJ McGill Univ, Montreal Gen Hosp, Med Clin, 1650 Cedar Ave, Montreal, PQ H3G1A4, Canada McGill Univ 1650 Cedar Ave Montreal PQ Canada H3G 1A4 4, Canada
Citazione:
A.J. Schwab e K.S. Pang, "The multiple indicator dilution method and its utility in risk assessment", ENVIR H PER, 108, 2000, pp. 861-872

Abstract

The multiple-indicator dilution (MID) technique entails the injection of amixture of labeled indicators into the blood vessel immediately at the entrance of an organ, e.g., the liver, kidney, heart, or lung, and characterization of outflow dilution profiles from timed venous samples. The mathematical basis of the method encompasses linear systems of partial differential equations that are formulated for flow- or barrier-limited transport combined with intracellular metabolism/excretion. The concept can be generalized to include metabolites. MID experiments are useful for determining tissue partition coefficients as well as kinetic parameters such as membrane permeabilities or metabolic/excretory intrinsic clearances, factors that affect the mean residence times or exposure of solutes to the organ. The main utility of the MID method lies in its role in identifying the basic mechanisms of the interaction of organs with vascular components. The concentration dependence in transport and removal is revealed by the rate coefficients upon varying the input concentrations of unlabeled substances into the organ at steady state. The data obtained with MID experiments can be incorporated into physiologically based pharmacokinetic (PBPK) models such as those used for biological risk assessment. This is especially pertinent in the case where diffusional barriers appear within organs. The insight gained from the MID organ approach may be useful for PBPK models with more realistic representation of organ kinetics.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 14:59:31