Blood clearance

General trends in radiopharmaceutical research emphasize the use of small peptides. These molecules, of which the agents mentioned for thrombosis localization are an example, exhibit rapid and specific binding, and rapid blood clearance, two important parameters for a successflil radiopharmaceutical. Peptides are readily labeled with Tc and lend themselves to formulation as lyophilized kits that can be rapidly and rehably reconstituted. Possible targets for these molecules are quite varied, ranging from atherosclerotic plaque to P-amyloid (for Alzheimer s disease), to a variety of somatic receptors the populations of which are increased or decreased in disease. 

Little is known regarding the pharmacokinetic properties of volatile nitrites in humans, particularly isobutyl nitrite and its primary metabolite, isobutyl alcohol. In rodents, after an intravenous infusion of isobutyl nitrite, blood concentrations peaked rapidly and then declined, with a half-life of 1.4 minutes and blood clearance rate of 2.9 L/min/kg (Kielbasa and Fung 2000). Approximately 98% of isobutyl nitrite is metabolized rapidly to isobutyl alcohol, concentrations of which also decline rapidly, with a half-life of 5.3 minutes. Bioavailability of inhaled isobutyl nitrite at a concentration of 300-900 ppm is estimated to be 43%. 

Ellens, H., Morselt, H. W. M., Dontje, B. H. J., Kalicharan, D., Hulstaert, C. E., and Scherphof, G. L. (1983). Effects of liposome dose and the presence of lymphosarcoma cells on blood clearance and tissue distribution of large unilamellar liposomes in mice, Cancer Res.. 43. 2927-2934. 

The clearance of an organ can be viewed as the volume of blood completely cleared of drug per unit time. Given this definition, the blood clearance of an organ... 

Singh, R. et al. (2006) Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers. Proceedings of the National Academy of Sciences of the U.S.A., 103 (9), 3357-3362. 

Ishida T, Kiwada H (2008) Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. Int J Pharm 354 56-62... 

Xu H, Wang KQ, Deng YH, da Chen W (2010) Effects of cleavable PEG-cholesterol derivatives on the accelerated blood clearance of PEGylated liposomes. Biomaterials 31 4757-4763... 

T5. Tygstrup, N., and Winkler, K., Galactose blood clearance as a measure of hepatic blood flow. Clin. Sci. 17, 1-9 (1958). 

It may be important to determine the degree of plasma protein and red blood cell binding of the test substance calculation of blood clearance rates using plasma or serum concentrations of the substance that have not been adjusted for the degree of binding may under or over-estimate the true rate of clearance of the test substance from the blood. This is usually done through experiments in vitro. 

Singh et al. (2006) investigated the tissue biodistribution and blood clearance rates of SWNTs in mice. Three different types of SWNTs were tested functionalized, water-soluble, and mIn-labeledDTPA-SWNT. All types exhibited a blood circulation... 

Laverman P, Carstens MG, Boerman OC, et al. Factors affecting the accelerated blood clearance of polyethylene glycol-liposomes upon repeated injection. J Pharmacol Exp Ther 2001 298 607. 

The blood clearance of the conjugates and free CDDP after intravenous injection was investigated. The conjugates and free CDDP were injected into male rat (6 weeks) intravenously. After specific periods, the amount of total Pt and free Pt in the blood was estimated by atomic absorption spectrometry before and after ultrafiltration (cut-off = 1.2 X 1(P), respectively. 

This approach assumes that the blood clearance profile of the dye follows an open one-compartment pharmacokinetics model. The characteristics of such a... 

Fig. 17. Comparison of blood clearance of glycoproteins and asialoglycoproteins. Removal of terminal sialic acid moieties by enzyme (neuraminidase) exposes the penultimate galactose moieties. The modified macromolecules are removed from the bloodstream very fast due to their biorecognition by the asialoglycoprotein receptor on hepatocytes. Based on data from [250]...

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