Dispersion model, clearance

Niro, R., Byers, J., Fournier, R., and Bachmann, K., Application of a convective-dispersion model to predict in vivo hepatic clearance from in vitro measurements utilizing cryopreserved human hepatocytes, Current Drug Metabolism, Vol. 4, No. 5, 2003, pp. 357-369. 

Other models of hepatic clearance include the sinusoidal model and the dispersion model. All these... 

Steady state the hepatic intrinsic clearance of pravastatin, a substrate for OATP2 and MRP2 (Tokui et al., 1999 Yamazaki et al., 1997), was regulated by the uptake process, followed by rapid metabolism and/or biliary excretion with minimal efflux to the systemic circulation in rats after infusion. The total hepatic elimination rate at steady state exhibited Michaelis-Menton saturation with the drug concentration and the and V ax obtained in rats with different mathematical models (i.e., well stirred, parallel tube, and dispersion models) were comparable with the initial uptake velocity measured from in vitro hepatocytes (Tokui et al., 1999). 

Yamamoto T, Itoga H, Kohno Y, Nagata K, Yamazoe Y. Prediction of oral clearance from in vitro metabolic data using recombinant CYPs Comparison among well-stirred, parallel-tube, distributed and dispersion models. Xenobiotica 2005 35 627-646. 

Tirona RG, Schwab AJ, Geng W, Pang KS. Hepatic clearance models comparison of the dispersion and Goresky models in outflow profiles from multiple indicator dilution rat liver studies. Drug Metab Dispos 1998 26 465-75. Bassingthwaighte JB, Sparks HV. Indicator dilution estimation of capillary endothelial transport. Anna Rev Physiol 1986 48 321-34. 

The water solubiUty of PLA-PEG and PLGA-PEG copolymers depends on the molecular weight of the hydrophobic (PLGA-PEG) and hydrophilic (PEG) blocks. Water soluble PLA-PEG copolymers with relatively low molecular weight PLA blocks self-disperse in water to form block copolymer micelles. For example, water soluble PLA-PEG 2 5 (M of PLA 2000 Da and M of PEG is 5000 Dalton) form spherical micelles 25 run in diameter. These micelles solubilize model and anticancer drugs by micellar incorporation. However, in vivo, the systemic lifetimes produced were relatively short and the clearance rate was signihcantly faster when the micelles are administered at low concentration. This suggests micellar dissociation at concentrations below the cmc. 

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