Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0393754 (HSA)
 2,996 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The bindings of perindopril and of its active metabolite perindoprilat to human serum, isolated proteins and to erythrocytes were studied by equilibrium dialysis. Within the therapeutic concentrations range, perindopril was 74% bound to serum involving a non-saturable process, NKa = 2.87. The main binders are serum albumin and alpha 1-acid glycoprotein. The serum binding of perindoprilat involved two successive steps. First, a saturable high-affinity binding (Ka: 2.8 x 10(9) M-1) occurred, involving probably the angiotensin converting enzyme (ACE). The second binding step was non-saturable with a very weak binding capacity, NKa = 0.15, quite superimposable to the HSA bound perindoprilat. Free fatty acids (FFA) did not alter the binding to HSA. The binding of both compounds to erythrocytes was low especially with perindopril, when measured in the presence of plasma. A significant correlation showed that the overall serum binding percentage of both drugs was essentially determined by HSA concentration. Serum binding was decreased in renal failure or cirrhosis, this result was principally linked to the hypoalbuminemia. Interactions with other drugs were limited to the binding of salicylate, tolbutamide and digitoxin to HSA.
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PMID:Specific and high affinity binding of perindoprilat, but not of perindopril to blood ACE. 133 Sep 41

In the present study equilibrium dialysis has been used to determine the degree of protein binding of the catecholamines adrenaline and noradrenaline and the adrenergic receptor blockers, prazosin and propranolol in diabetics. The binding of the catecholamines in plasma from Type I and II diabetic patients was not significantly different from that of healthy subjects. The ratio of the bound and free catecholamine concentrations was correlated with the level of albumin (HSA). Significantly reduced protein binding of prazosin was observed in Type I and II diabetic subjects compared to healthy volunteers. The binding of propranolol was significantly reduced in Type I patients. The ratios between the bound and unbound concentrations of prazosin and propranolol were significantly correlated with the levels of alpha 1-acid glycoprotein (AAG). The results suggest that non-enzymatic glycosylation of plasma proteins may increase the unbound fraction of the adrenergic blockers prazosin and propranolol.
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PMID:Plasma protein binding of catecholamines, prazosin and propranolol in diabetes mellitus. 142 89

1. Serum protein binding of isradipine and darodipine, and serum concentrations of alpha 1-acid glycoprotein (AAG), albumin (HSA) and non-esterified fatty acids (NEFA) were measured in three groups of patients, I: healthy subjects (n = 20); II: patients with inflammatory disorders (n = 15) and III: patients with hepatic insufficiency (n = 17). 2. AAG was increased significantly in group II patients (P less than 0.001) and decreased in group III patients (P less than 0.001); HSA was decreased significantly in group II and group III patients (P less than 0.001). 3. The free percentage of isradipine was decreased significantly in group II patients (P less than 0.05) and increased in group III patients (P less than 0.05) and multivariate analysis showed that these variations were inversely related to changes in AAG concentration. 4. The free percentage of darodipine was increased significantly in group II and III patients (P less than 0.05) due to a decrease in HSA concentration, as shown by multivariate analysis. 5. The changes in free serum percentages of isradipine and darodipine were inversely related to concomitant changes in the concentration of the serum protein for which they showed the highest affinity, AAG for isradipine and HSA for darodipine, respectively. 6. The unexplained variability in the binding data was greater when AAG was the major determinant of binding (isradipine).
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PMID:Differences in the serum binding determinants of isradipine and darodipine--consequences for serum protein binding in various diseases. 253 7

1. The effect of variable alpha 1-acid glycoprotein (AAG) and albumin (HSA) concentrations on the binding of prazosin and propranolol was assessed in plasma after surgery and in mixtures of AAG/HSA with concentrations mimicking those found in vivo. 2. On the pre-operative day the binding of prazosin and propranolol was 94.8% and 89.0%, respectively and 97.3% and 93.2%, respectively, 5 days after surgery. 3. In solutions containing mixtures of highly purified AAG and HSA representing the pre-operative state, 88.6% and 83.9% binding of prazosin and propranolol was observed, whereas for solutions mimicking post-operative plasma, the equivalent values were 94.6% and 91.4%, respectively. 4. The ratios between bound and unbound concentrations of both drugs were closely correlated to the concentrations of AAG, but not to the concentrations of HSA. 5. The present study demonstrates that AAG is responsible for the binding variability of prazosin and propranolol in plasma from post-operative patients.
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PMID:Binding of prazosin and propranolol at variable alpha 1-acid glycoprotein and albumin concentrations. 271 17

Propranolol binding to human albumin (HSA) and to mixtures of alpha 1-acid glycoprotein (AGP) and HSA was examined in the presence of a perfluorochemical (PFC) blood substitute. The per cent free propranolol was determined using a dialysis exchange method at 37 degrees C. In 4% HSA solutions the per cent free propranolol was 51.9% and 53.6% at propranolol concentrations of 100 and 500 ng/ml, respectively. Buffer dilutions of 4% HSA solutions resulted in an increase in free propranolol. However, dilution of the HSA solutions with the PFC emulsion resulted in a significant decrease in free propranolol. In solutions containing 4% HSA with 0.067% AGP, the per cent free propranolol was 22.6% and 23.5% for 100 and 500 ng/ml propranolol, respectively. Again, the per cent free propranolol increased upon plasma protein dilution with buffer solution and decreased upon dilution with the blood substitute. A centrifugation method was utilized to determine the per cent bound propranolol associated with the PFC emulsion droplets in the presence of the proteins. Propranolol was significantly bound by the PFC emulsion even in the presence of a mixture of AGP and HSA. These results indicate that the overall affinity of the PFC blood substitute for propranolol is very substantial. Thus, administration of this PFC blood substitute may not result in the significant increase in per cent free propranolol normally associated with plasma protein dilution.
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PMID:Human albumin and alpha 1-acid glycoprotein binding of propranolol in the presence of a perfluorochemical blood substitute. 273 Feb 40

Prazosin is extensively bound in human serum/plasma. In the present study a bound fraction of 93-95% was observed at 37 degrees for therapeutic drug concentrations. Both alpha 1-acid glycoprotein (AAG) and albumin (HSA) are established as transport proteins for prazosin, but their individual contribution to the extent and variability of protein binding in serum/plasma is unclear. The present study showed that AAG possesses one binding site per molecule with high affinity (Kd approximately 0.8 microM) for prazosin. HSA, essentially globulin-free, bound prazosin with lower affinity (Kd approximately 30 microM) with an average of 0.3 binding sites per molecule. However, less purified HSA, containing globulins, exhibited apparently higher affinity (Kd approximately 8 microM), but lower binding capacity (0.07 sites per molecule) for prazosin. In mixtures of highly purified proteins, the concentrations of AAG, and not HSA, determined the extent and variability of prazosin binding.
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PMID:Binding of prazosin to alpha 1-acid glycoprotein and albumin: effect of protein purity and concentrations. 274 45

Cell sorting and cytotoxic depletion procedures were used to subdivide the population of CD4- CD8- ("double-negative") thymocytes from adult CBA mice on the basis of expression of Ly-1, HSA (the "heat-stable antigen" M1/69 or B2A2), Pgp-1 glycoprotein, Thy-1, MEL-14 and the PC61 antigenic determinant on the IL2 receptor (IL2R). The level of dividing cells within these subsets was assessed by brief in vivo administration of [3H]-thymidine, followed by radioautography, or by flow cytometric cell cycle analysis after DNA staining. The capacity of the subsets to proliferate in culture, in response to stimulation with concanavalin A (Con A), or with phorbol myristate acetate (PMA) and the calcium ionophore ionomycin, was assessed in high cloning efficiency single-cell culture systems. In general, the proliferative response in culture was inversely related to the rate of cell division in vivo. Response of the double-negative subsets to Con A correlated with expression of the T cell antigen receptor complex; although a high cloning efficiency was obtained from the receptor-positive fractions, very few of the clones were cytotoxic. In particular, a major Ly-1+ HSA- Pgp-1+ double-negative subset, as well as minor Ly-1- HSA- Pgp-1+ subsets, contained very few cells in cycle in vivo, but showed a high cloning efficiency in both culture systems. Conversely, the other major double-negative subset, Ly-1- HSA+ Pgp-1-, included most of the cells in cycle, but showed a reduced cloning efficiency in response to PMA and ionomycin and failed to respond to Con A. The dividing cells within the Ly-1- HSA+ Pgp-1- group were strongly enriched in the IL2R- rather than in the IL2R+ subset, suggesting IL2 was not the growth factor maintaining their proliferation in vivo.
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PMID:Subpopulations of CD4- CD8- murine thymocytes: differences in proliferation rate in vivo and proliferative responses in vitro. 289 96

The serum concentrations of alpha 1-acid glycoprotein (AAG), albumin (HSA) and non-esterified fatty acids, and the serum binding of tertatolol were measured in four groups of individuals: healthy control subjects (n = 24), and patients with inflammation (n = 28), and hepatic (n = 20) and renal (n = 27) insufficiency. Serum binding of tertatolol was increased in patients with inflammation (94.6%), decreased in patients with hepatic insufficiency (88.8%) and it was unchanged in patients with renal insufficiency (92.8%) as compared to controls (92.7%). Multivariate analysis indicated that the changes were mainly related to concomitant changes in AAG concentration, which could account for 57% of intersubject variability in the bound/free ratio, and to a lesser extent in HSA, which accounted for only 4% of the variability in the binding. The data show that the free fraction of the basic drug tertatolol in serum is affected by pathological conditions that cause changes in AAG concentration.
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PMID:Variation in serum binding of tertatolol mediated by disease-induced modification of alpha-acid glycoprotein concentration. 290 Jan 45

Propranolol binding to isolated human alpha-1-acid glycoprotein (AGP) and human albumin (HSA) was studied by equilibrium dialysis at 37 degrees C. With AGP (0.067%) and HSA (4%), total propranolol concentration was varied from 0.7 to 93,000 ng mL-1. Over this concentration range the percentage drug bound to HSA declined from 49 to 39% while that to AGP declined from 68 to 4%. Two classes of sites were identified on AGP with n1k1 = 8.50 X 10(4) M-1 and n2k2 = 3.12 X 10(4) M-1. With a pH 7.4 phosphate buffer, propranolol binding to AGP was greatest when the protein was initially dissolved in pH 7.4 water compared with pH 7.2 water or the phosphate buffer. Thus, the method of AGP solution preparation affected propranolol binding by this protein. For both AGP and HSA, greater drug binding was noted with phosphate buffers in comparison with a physiological buffer. With phosphate buffers, decreasing pH from 7.4 to 7.0 decreased propranolol binding by AGP, while decreasing pH from 7.7 to 7.4 had little effect. With HSA, the percent propranolol bound consistently decreased on lowering pH from 7.7 to 7.0.
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PMID:Buffer and pH effects on propranolol binding by human albumin and alpha 1-acid glycoprotein. 290 83

The present study was undertaken to decide whether the bound fractions and/or total concentrations of catecholamines were determinative for the variability of biologically active concentrations in human plasma. The binding and concentrations of noradrenaline (NA) and adrenalin (Adr) were determined in acute phase plasma after major hip surgery in five subjects. The bound fractions before surgery were 23.0% and 18.4% for NA and Adr, respectively. The binding of catecholamines increased in the post-operative period. Five days after surgery the binding of NA and Adr was 30.9% and 24.0%, respectively. The surgical trauma induced an acute phase reaction in plasma with a decrease of albumin (HSA) concentrations whereas the concentrations of alpha-1 acid glycoprotein (AAG) increased. The catecholamine concentrations showed a considerable inter- and intraindividual variability. However, the present work shows that the variability of the biologically active catecholamine concentrations is mainly dependent on the total plasma concentrations and not the plasma protein binding.
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PMID:Catecholamine binding and concentrations in acute phase plasma after surgery. 314 32


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