Plasma proteins retention

Sawada and coworkers [25-27] studied the iso-pH 7.4 MDCK permeabilities of very lipophilic molecules, including chlorpromazine (CPZ) [25], These authors included 3% wt/vol bovine serum albumin (BSA) on the apical (donor) side, and 0.1-3% BSA on the basolateral (acceptor) side, and found that plasma protein binding greatly affected the ability of molecules to permeate cellular barriers. They observed cell tissue retention of CPZ ranging from 65 to 85%, depending on the... 

There have been several reports where plasma protein binding data was used in the prediction of in vivo properties of compounds. Two papers noted that the ability to predict in vivo clearance from in vitro microsome data was greatly improved when a plasma protein binding term was included [64,65]. In another study, binding to phospholipids and human serum albumin was assessed by HPLC retention times (on IAM and HAS columns, respectively) and used to predict volume of distribution [66]. 

Statistical Methods. Means of treatment groups for plasma retention of BSP, plasma osmolality, total plasma protein concentration and urine flow rates were compared by students t test for independent sample means (17). Plasma enzyme activity data were converted to a quantal form and analyzed by the Fischer Exact Probability Test (18). Values greater than 2 standard deviations (P < 0.05) from the control value were chosen to indicate a positive response in treated fish. 

Nephrotic syndrome is characterized by proteinuria and edema due to some form of glomerulonephritis. The resulting fall in plasma protein concentration decreases vascular volume, which leads to diminished renal blood flow. This in turn causes secondary aldosteronism characterized by Na and water retention and K+ depletion. Rigid control of dietary Na is essential. Therapy of the nephrotic syndrome using a thiazide (possibly with a K -sparing diuretic) to control the secondary aldosteronism, is a useful initial approach to treatment Since nephrotic edema is frequently more difficult to control than cardiac edema, it may be necessary to switch to a loop diuretic (and spironolactone) to obtain adequate diuresis. 

Cyclophosphamide can be given orally, intramuscularly, or intravenously. The plasma half-life of intact cyclophosphamide is 6.5 hours. Only 10 to 15% of the circulating parent drug is protein bound, whereas 50% of the alkylating metabolites are bound to plasma proteins. Since cyclophosphamide and its metabolites are eliminated primarily by the kidneys, renal failure will greatly prolong their retention. 

The packing material first described for direct injection of biological samples was prepared by simply saturating the accessible adsorption sites of a Cis reversed-phase silica with human plasma proteins (105). After saturation, the human plasma proteins were denatured at the external surface, and their native conformation was destroyed. With this treatment, the proteins formed a hydrophilic layer with weak ion-exchange properties, which provided protection from contact with the sample proteins, whereas the alkyl ligands inside the pores remained unchanged and thus served for analyte retention. The retention behavior of the saturated phase did not alter with this treatment, but the efficiency was reduced dramatically. Such protein-coated columns have shown a lifetime of several months (106). 

These particles and macromolecules are both characterized by a large size, which increases their blood retention by avoiding glomerular filtration. They behave pharmacokinetically similarly to plasma proteins. 

Alfentanil is 90% protein bound, and variabUity in protein binding can affect its actions. In 10 patients who received standardized anesthesia and alfentanil to a target concentration of 150 ng/ml for postoperative analgesia interindividual variation in plasma protein binding explained at least 39% of the interindividual variability in alfentanil requirements (13). There was a high incidence of adverse effects seven patients had emesis and five had urinary retention. 

With prolonged bed rest, fluid retention occurs and plasma protein and albumin concentrations may be decreased by an average of 0.5 and 0.3g/dL, respectively. The concentrations of protein-bound constituents are also reduced, although mobilization of calcium from bones with an increased free ionized fraction compensates for the reduced protein-bound calcium, so serum total calcium is less affected. Serum aspartate aminotransferase activity is usually slightly less in individuals confined to bed than in those undertaking normal physical activity. Initially and paradoxically, creatine kinase (CK) activity is increased as a result of its release from skeletal muscles, but ultimately, CK activity may be less than in active, healthy individuals. Serum potassium may be reduced by up to 0.5mmol/L because of reduction of skeletal muscle mass. 

Fluid retention caused by nicotine causes a mild decrease in the plasma protein concentration but without demonstrable effect on the calcium concentration or on the activity of serum enzymes. The plasma urate concentration is less in smokers than in nonsmokers, probably as a result of lessened intake of food by smokers. Both the serum urea and creatinine concentrations tend to be less in smokers than in nonsmokers. 

The total protein concentration of serum obtained from a healthy ambulatory adult is 6.3 to 8.3 g/dL and 6.0 to 7.8 g/dL from an adult at rest. The two general causes of alterations of serum total protein are a change in the volume of plasma water and a change in the concentration of one or more of the specific proteins in the plasma. Decrease in the volume of plasma water (hemoconcentration) is reflected as relative hyperproteinemia concentrations of all the individual plasma proteins are increased. Hyperproteinemia is noted in dehydration caused by inadequate water intake or excessive water loss as in severe vomiting, diarrhea, Addison s disease, or diabetic acidosis. Hemodilution (increase in plasma water volume) is reflected as relative hypoproteinemia concentrations of aU the individual plasma proteins are decreased. Hemodilution occurs with water intoxication or salt retention syndromes, during massive intravenous infusions, and physiologically when a recumbent position is assumed. A recumbent position decreases total protein concentration by 0.3 to 0.5 g/dL and many individual proteins including albumin by up to 10%. 

In renal failure, organic acids, phosphate, and sulfate are increased because of retention. Chronic metabolic acidosis enhances mobilixation of calcium from bone the decrease in plasma pH increases dissociation of plasma protein-bound calcium so that more Ca is filtered through the glomerulus and less is reabsorbed in the tubule (see also Chapter 45). 

Tc-DPD shows lower binding to plasma protein and is excreted to a smaller extent in the urine (Schwarz et al. 1991). Whole-body retention at 24 h was 40.6% for DPD and 27.0% in the case of MDP (Buell et al. 1982). The bone-to-soft tissue ratio, which is important for skeletal scintigraphy, showed consistently higher values for Tc-DPD, namely, an increase of 11.4% in normal volunteers and 7.3% in patients 2 h postinjection (Buell et al. 1982). 

Several polymers were evaluated in the form of a surface coating on glass beads packed in columns to determine their ability to retain platelets when whole human blood passes over the surface. This ability was measured as the platelet retention index p, the fraction of platelets retained on the column. Lowest values of p were found for poly(ethylene oxide), polypropylene oxide), poly(tetramethylene oxide) (in the form of polyurethanes), and polydimethylsiloxane. Highest values (around 0.8) were found for cross-linked poly(vinyl alcohol) and the copolymers of ethylenediamine with diisocyanates. Intermediate values were found for polystyrene and its copolymers with methyl acrylate, for polyacrylate, and for poly(methyl methacrylate). The results are interpreted in terms of possible hydrophobic and hydrogen bonding interactions with plasma proteins. 

This chapter deals with a specific test of blood-surface interaction in vitro platelet retention in a column of beads (due to platelet adhesion and aggregation). Protein adsorption precedes platelet adsorption, and thus the in vitro platelet retention test involves competitive and sequential adsorption of proteins, the outcome of which produces surfaces having widely varying degrees of platelet retention. Except in the case of thrombin (3), plasma protein absorption on these surfaces has not been studied. 

The evidence summarized in Figure 2 shows lowest platelet retention indices for polyethylene oxide) (PEO), polypropylene oxide) (PPO), and PDMS. This result implies low degrees of adsorption of specific critical plasma proteins and/or adsorption without conformation alteration of the protein. The molecular attributes these three polymers have in common appear to be ... 

Intestinal absorption of Ge dioxide (Ro-senfeld 1954) or alkyl Ge is both rapid and efficient (>90%) (Vouk 1986). Inhaled elemental Ge dust is also readily taken up by the body. Once absorbed, Ge is not bound to plasma protein, but is widely distributed through the body, without any strong selective retention in any particular tissue or organ (Lee 1998). 

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