Serum proteins, drug binding

It is well known that drugs bind to plasma proteins, particularly to serum albumin and a-acid glycoprotein, and that only the unbound, or free, fraction is responsible for any pharmacological effect. For protein-drug binding studies size-exclusion chromatography in one of three variants—namely, the Hum-mel-Dreyer method (1962), the vacancy peak method (Sebille, et al., 1979), and frontal analysis (Cooper and Wood, 1968)—is the traditional method of... 

Since lipophilic molecules have affinity for both the membrane lipid and the serum proteins, membrane retention is expected to decrease, by the extent of the relative lipophilicities of the drug molecules in membrane lipid versus serum proteins, and by the relative amounts of the two competitive-binding phases [see Eqs. (7.41)-(7.43)]. Generally, the serum proteins cannot extract all of the sample molecules from the phospholipid membrane phase at equilibrium. Thus, to measure permeability under sink conditions, it is still necessary to characterize the extent of membrane retention. Generally, this has been sidestepped in the reported literature. 

Medication Transportation interactions. Recall that carrier proteins in the bloodstream escort medications and that over 80% of the circulating concentration of most psychiatric medicines is bound to serum proteins. When there are not enough protein binding sites to go around, however, the biologically active free fraction of the drug is increased. 

Kraak et al. (38) reported the first ACE application to study drug binding to a plasma protein. They used the model system warfarin-human serum albumin (HSA) to compare the suitability of the Hummel-Dreyer, frontal analysis, and vacancy peak methods. A more methodologically intended paper from Erim and Kraak (39) used VACE to study the displacement of warfarin from bovine serum albumin (BSA) by furosemide and phenylbutazone. They concluded that VACE is especially suited to examining competitive properties of simultaneously administered compounds toward a given protein-drug system. 

MG Quaglia, E Bossu, C DellAquila, M Guidotti. Determination of the binding of a /32-blocker drug, frusemide and ceftriaxone to serum proteins by capillary zone electrophoresis. J Pharm Biomed Anal 15 1033—1039, 1997. 

Drug, Trade Name Preferred Route Serum half-life (hr) Serum protein binding (%)... 

Isoniazid does not bind to serum proteins it diffuses readily into all body fluids and cells, including the caseous tuberculous lesions. The drug is detectable in significant quantities in pleural and ascitic fluids, as well as in saliva and skin. The concentrations in the central nervous system (CNS) and cerebrospinal fluid are generally about 20% of plasma levels but may reach close to 100% in the presence of meningeal inflammation. 

For drugs that bind to serum proteins, equilibrium exists between the bound or ineffective portion and the unbound (free) or effective portion. For acidic drugs that are highly bound to albumin, the free plasma concentration may correlate best with pharmacologic effect. Although albumin levels decrease only slightly with age, they tend to decrease during periods of illness. This can result in elevated levels of... 

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