Plasma binding

The free plasma fraction (fp) determines the relation between free, bound ( plasma binding PB%), and total concentration. 

Distribution. Lead in blood partitions between plasma and red blood cells, with the larger fraction (90-99%) associated with red blood cells (Cake et al. 1996 DeSilva 1981 Everson and Patterson 1980 Manton and Cook 1984 Ong and Lee 1980a). Lead in plasma binds to albumin and y -globulins (Ong and Lee 1980a). The fraction that is not bound to protein exists largely as complexes with low molecular weight sulfhydryl compounds these may include cysteine, homocysteine, and cysteamine (Al-Modhefer et al. 1991). Approximately 75% was bound to protein when whole human blood was incubated with 50 ig/dL lead (as lead chloride) approximately 90% of the bound lead was associated with albumin (Ong and Lee 1980a). However, the fraction of lead in plasma bound to protein would be expected to vary with the plasma lead concentration. 

Walgren, R. A., Walls, T., The influence of plasma binding on absorption/exsorption in the Caco-2 model of human intestinal absorption, J. Pharm. Pharmacol. 1999, 52, 1037— 1040. 

An X-ray crystal structure of 28 bound in the thumb-region of the NS5B polymerase showed little interaction of the acetamide moiety with the protein. Alterations at this position were explored in order to improve the physical properties of the compound. Incorporation of basic amines as part of this side-chain, leading to zwitterionic compounds, reduces plasma binding and has a beneficial effect on cell activity and pharmacokinetic profiles. In the cell-based replicon assay, racemic 29 has an EC50 of 152 nM in the presence of 10% fetal calf serum and 376 nM in the presence of 50% normal human serum [71],... 

Allometry (fractal VD) Body volume and weight are related across species, tissue and plasma binding is similar across species VDSS in two or more animal species [8]... 

The inhalation route for administering drugs into the pulmonary system for treatment of respiratory diseases eliminates many bioavailability problems such as plasma binding and first-pass metabolism, which are encountered in parenteral or oral administration. Consequently, a small inhalation dose is adequate for achieving... 

Plasma binding - both the quantity and types of proteins in plasma differ in these classes of animals. Mammals tend to have large amounts of protein compared with fish (ca. 8 vs 3 g/100 ml) and albumin, the protein which binds most xenobiotics, is negligible in a number of fish species. 

Competition between drugs for plasma binding sites occurs and is responsible for some of the clinically most important changes in drug distribution. Phenylbutazone and oxyphenbutazone, for example, potentiate the action of warfarin by displacement (A2) and trichloroacetic acid, a major metabolite of chloral hydrate has a similar effect (S12) and is the cause of hemorrhagic complications during coumarin therapy (A2). 

Pharmacokinetics The parietal cells of the stomach secrete intrinsic factor, which regulates the amount of vitamin B-12 absorbed in the terminal ileum. Bioavailability of oral preparations is approximately 25%. Vitamin B12 is primarily stored in the liver. Enterohepatic circulation plays a key role in recycling vitamin B-12 from mainly bile. If plasma-binding proteins are saturated, excess free vitamin B- 2 will be excreted in the kidney. 

Since VD is a function of relative tissue and plasma binding, it follows that if these measurements could be made in vitro, then the data could be used to predict VD. Furthermore, if tissue binding is driven by physicochemical properties, such as lipophilicity, then it also follows that physicochemical measurements could serve as surrogates for tissue binding propensity. In vitro tissue binding and physicochemical measurements form the basis of in vitro approaches to predict human VD. 

Simon, N., DaiDy, E., Combes, O., Malaurie, E., Lemaire, M., Tdlement, J.P. and Urien, S. (1998) Role oflipoproteins in the plasma binding of SDZ PSC 833 a novel multidrug resistance-reversing cyclosporin. British Journal of Clinical Pharmacology, 45, 173-175. 

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