Glycoproteins plasma proteins

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

The concentration of total protein in human plasma is approximately 7.0-7.5 g/dL and comprises the major part of the solids of the plasma. The proteins of the plasma are actually a complex mixture that includes not only simple proteins but also conjugated proteins such as glycoproteins and various types of lipoproteins. Thousands of antibodies are present in human plasma, though the amount of any one antibody is usually quite low under normal circumstances. The relative dimensions and molecular masses of some of the most important plasma proteins are shown in Figure 50-1. 

Section VI consists of discussions of eleven special topics nutrition, digestion, and absorption vitamins and minerals intracellular traffic and sorting of proteins glycoproteins the extracellular matrix muscle and the cy-toskeleton plasma proteins and immunoglobulins hemostasis and thrombosis red and white blood cells the metabolism of xenobiotics and the Human Genome Project. 

The basement membrane is an acellular meshwork consisting of collagen and glycoproteins. The collagen provides structural support and the negatively charged glycoproteins prevent the filtration of plasma proteins into Bowman s capsule. 

There have been several studies that underscore the importance of unbound concentration in cell-based studies of receptor function. In a model study of the effect of plasma protein binding on the renal transport of organic anions using the expression of various organic anion transporters (OATPs) in Xenopus oocytes, the transport of ochratoxin A, methotrexate, and estrone sulfate was found to be strongly inhibited by the addition of human serum albumin to the culture medium [16]. Similarly, the addition of oq-acid glycoprotein was found to reverse the blockade of sodium-ion current by cocaine in a preparation of cardiac myocytes [17]. 

Finally, work that may facilitate understanding the role of oq-acid glycoprotein variants in inter-individual variations in plasma protein binding, pharmacokinetic behavior, and drug action has been described. A capillary zone electrophoresis method that allows for the determination of 11 intact forms (i.e., isoforms, glycoforms) of oq-acid glycoprotein has been described [84],... 

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