salicylates and Uremia

Topics: Albumins; Barbiturates; Carbon; Cellulose; Collodion; Creatinine; Embolism; Hemadsorption; Microscopy, Electron, Scanning; Poisoning; Salicylates; Thrombocytopenia; Uremia

Topics: Acute Kidney Injury; Barbiturates; Brain Edema; Humans; Hyperkalemia; Methanol; Methods; Osmolar Concentration; Osmotic Pressure; Peritoneal Dialysis; Poisoning; Pulmonary Edema; Salicylates; Time Factors; Uremia

Topics: Administration, Oral; Adrenal Cortex Hormones; Animals; Anti-Bacterial Agents; Anticoagulants; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Factors; Clofibrate; Coumarins; Diuresis; Dogs; Heparin; Humans; Hypnotics and Sedatives; Liver Diseases; Metabolic Diseases; Phenylbutazone; Rats; Salicylates; Sulfonamides; Thrombosis; Uremia; Vitamin K

DanShen is a Chinese medicine that is used to treat cardiovascular disorders. DanShen is moderately to strongly protein bound, mainly to albumin. Because impaired protein binding of albumin-bound drugs in uremia has been reported, we studied protein binding of DanShen by measuring the digoxin-like immunoreactive component of this Chinese medicine. We observed a significantly higher percentage of free fraction of DanShen in uremic sera in vitro. Impaired protein binding of DanShen was also observed in sera from patients with liver disease, who had elevated concentrations of bilirubin. Treating uremic sera with activated charcoal significantly improved the protein binding of DanShen, indicating that uremic compounds are responsible for the impaired protein binding of DanShen. On the other hand, when various amounts of bilirubin were added to aliquots of the normal pool supplemented with DanShen, we observed only a modest displacement of DanShen from the protein-binding sites by bilirubin, indicating that hypoalbuminemia may play a major role in impaired protein binding of DanShen in sera with elevated bilirubin concentrations. We conclude that protein binding of DanShen is lower in uremic sera and in sera with elevated bilirubin concentrations.

Topics: Acetates; Benzenesulfonates; Bilirubin; Blood Proteins; Charcoal; Creatine; Digoxin; Drugs, Chinese Herbal; Fluorescence Polarization Immunoassay; Humans; Hyperbilirubinemia; Phenanthrolines; Protein Binding; Salicylates; Salvia miltiorrhiza; Serum Albumin; Uremia

Displacement of phenytoin and valproic acid by salicylate have been described. We studied carbamazepine-salicylate interactions in normal and uremic sera, which have not been studied. Salicylate caused significant displacement of carbamazepine from protein binding, leading to higher concentrations of free carbamazepine. The concentrations of free carbamazepine were always significantly higher in uremic sera than in normal sera. However, when uremic sera were supplemented with both carbamazepine and salicylate, we observed a much lower displacement of carbamazepine and only a slight increase in free carbamazepine concentration. Treatment of uremic sera with activated charcoal corrected the binding deficiency for carbamazepine. Known uremic compounds like hippuric acid and indoxyl sulphate can only partly explain the observed displacement of carbamazepine in uremic sera. We conclude that salicylate displaces carbamazepine from protein binding in normal sera, but this interaction is significantly reduced in uremic sera.

Topics: Carbamazepine; Drug Interactions; Hippurates; Humans; Salicylates; Salicylic Acid; Sulfates; Uremia

Limited studies indicate increased free fraction of valproic acid in uremia. One study also described displacement of valproic acid from protein binding by salicylate in children with epilepsy. The authors studied in vitro interaction of valproic acid and salicylate in uremic sera and compared their results with same interactions in normal sera. As expected, the concentrations of free valproic acid were always significantly higher in uremic sera compared with normal sera. When uremic sera were supplemented with both valproic acid and salicylate, a much lower displacement of valproic acid by salicylate was observed, compared with the effects observed in normal sera. Treatment of uremic sera with charcoal removed those uremic compounds, and the concentration of free valproic acid in charcoal-treated uremic sera were comparable to the concentrations observed in normal sera. When uremic compounds were extracted from charcoal with methanol, lyophilized, and added to normal serum, an increase in free valproic acid concentration in normal serum was observed, indicating that uremic compounds, rather than altering albumin structure, are responsible for elevated free valproic acid concentration in uremia. However, uremic extract failed to produce any further displacement of valproic acid in normal serum in the presence of salicylate. The authors concluded that uremic compounds are responsible for elevated free valproic acid concentrations, but the displacement of valproic acid by salicylate in uremic sera are less remarkable compared with such effect in normal sera.

Topics: Charcoal; Drug Interactions; Humans; In Vitro Techniques; Protein Binding; Salicylates; Salicylic Acid; Uremia; Valproic Acid

Impaired binding of anionic drugs to serum albumin in patients with uremia is thought to be due to the accumulation of endogenous substances that bind to albumin. In this study the displacement by the anionic drugs diazepam, warfarin, and salicylic acid, which are known to be representative drugs for the binding sites on the albumin molecule, of several endogenous ligands that bind to albumin in uremic serum was examined. The free fractions of the ligands bound to albumin were separated by ultrafiltration in the presence and the absence of test drugs and assayed by high-performance liquid chromatography. Diazepam displaced indoxyl sulfate (IS), hippuric acid (HA), and indole-3-acetic acid (IAA), and warfarin displaced IS, HA, ISAA, and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid from serum albumin. However, salicylic acid did not displace the substance examined. The methods reported here are useful for determining the binding sites of the endogenous ligands on albumin and to clarify the drug-ligand interaction on albumin molecule in uremic serum.

Topics: Binding Sites; Furans; Hippurates; Humans; Indican; Indoleacetic Acids; Propionates; Protein Binding; Salicylates; Salicylic Acid; Serum Albumin; Uremia; Warfarin

We quantified indoxyl sulfate in uremic serum by using internal-surface reversed-phase high-performance liquid chromatography. Its concentrations were markedly increased in chronic hemodialysis patients, and were significantly but weakly correlated with the concentrations of creatinine and beta 2-microglobulin in these patients' serum, and with the duration of their hemodialysis treatment. Indoxyl sulfate could not be removed effectively by conventional hemodialysis because of its strong binding to serum albumin. Equilibrium dialysis demonstrated that indoxyl sulfate inhibited the binding of salicylate to albumin, and that 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid inhibited the binding of indoxyl sulfate to albumin. In conclusion, indoxyl sulfate was markedly accumulated in uremic serum, and inhibited drug binding.

Topics: Albumins; beta 2-Microglobulin; Chromatography, High Pressure Liquid; Furans; Humans; Indican; Propionates; Renal Dialysis; Salicylates; Uremia

3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, 3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid, 3-carboxy-4-methyl-5-ethyl-2-furanpropionic acid and 3-carboxy-5-propyl-2-furanpropionic acid were detected in uremic serum using gas chromatography-mass spectrometry. Mass chromatography revealed that the serum concentrations of the furancarboxylic acids especially 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, were increased in the chronic hemodialysis patients and that the acids could not be removed by conventional hemodialysis due to their strong binding to plasma protein. 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid was also quantitated in uremic serum by high-performance liquid chromatography. Serum level of the acid in uremic patients showed significant but weak correlation with serum level of urea and duration on hemodialysis. Equilibrium dialysis demonstrated that 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid and 3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid inhibited the bindingof salicylate and 5,5-diphenylhydantoin to albumin. In conclusion, the furancarboxylic acids especially 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid were accumulated in uremic serum as inhibitors of drug binding.

Topics: Adult; Aged; Carrier Proteins; Chromatography, High Pressure Liquid; Female; Furans; Gas Chromatography-Mass Spectrometry; Humans; In Vitro Techniques; Male; Middle Aged; Propionates; Renal Dialysis; Salicylates; Serum Albumin; Uremia

We have evaluated pH, chloride, calcium and several endogenous aromatic acids as possible causes of the impaired binding of drugs by plasma albumin in renal failure. Changes in pH, chloride and calcium over the range found in renal failure had minimal or no effects on the binding of [14C]salicylate, a model probe which binds to both of the major drug-binding loci of human albumin. Hippurate and indoxyl sulfate were weak inhibitors of binding by normal plasma. Ortho-hydroxy-hippurate was undetectable or minimally elevated, except among patients with elevated plasma salicylate concentration. Although plasma hippurate and indoxyl sulfate concentrations were elevated markedly in patients with renal failure, inhibition of salicylate binding was significantly correlated only with the concentration of indoxyl sulfate. Addition of hippurate and indoxyl sulfate separately and together to normal plasma showed that these ligands could account for only 15% of the impaired binding of salicylate by azotemic plasma. The retained solutes which account for most of this binding defect remain to be identified. This uremic disorder (and perhaps others) is due not to a single chemical but to the additive effect of a family of chemicals.

Topics: Blood Proteins; Calcium; Chlorides; Creatinine; Hippurates; Humans; Indican; Kidney Failure, Chronic; Ligands; Salicylates; Salicylic Acid; Uremia

Topics: Blood Proteins; Hippurates; Humans; Indican; Protein Binding; Salicylates; Salicylic Acid; Toxins, Biological; Uremia

Topics: Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Glucuronates; Hippurates; Humans; Molecular Weight; Salicylates; Salicylic Acid; Toxins, Biological; Uremia

A simple, rapid, and sensitive method for the determination of aspirin and salicylic acid in plasma of uremic patients is reported. After extraction with hexane, aspirin (ASA) and salicylic acid (SA) were quantified by high-performance liquid chromatography (HPLC) with ultraviolet detection at 229 nm. ASA and SA concentrations and peak-height ratios were linearly related up to 20 micrograms/ml. The lower limit of sensitivity was 0.1 microgram/ml for both compounds. The average recoveries of aspirin and salicylic acid were 27 and 54%, respectively. This procedure offers better performance than do previously described methods. The sample clean-up allows quantitation of a low concentration of aspirin in uremic patients' plasma, commonly rich in interfering endogenous substances.

Topics: Aspirin; Chromatography, High Pressure Liquid; Humans; Salicylates; Salicylic Acid; Uremia

An efficient separation of middle molecules (Mr 350-2000) was obtained by gel permeation HPLC and ion exchange HPLC. These methods were used to analyze glucuronyl-o-hydroxyhippurate (GOHH), a metabolite previously identified in plasma and urine from uremic patients. The concentrations of GOHH in normal and uremic urine and in uremic plasma increased markedly after the ingestion of salicylate. Oral ingestion of phenylalanine and tyrosine did not influence GOHH in plasma and urine. The results indicate that GOHH is an endogenous metabolite in normal and uremic subjects, as well as a novel metabolite of salicylate.

Topics: Chromatography, Gel; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Glucuronates; Hippurates; Humans; Molecular Weight; Salicylates; Salicylic Acid; Uremia

To provide insight into the reported reduction in the plasma clearance of diflunisal in human renal failure, this investigation evaluated several possible mechanisms for this effect in experimental renal failure. Rats with renal failure, induced by uranyl nitrate or by ureteral ligation, had both a lower plasma clearance and an increased apparent volume of distribution, a pattern resembling that seen in human renal failure. Steady-state diflunisal concentration and unbound fraction were determined in studies during a constant infusion of diflunisal to establish the relationships of concentration, protein binding and intrinsic clearance. The infusion studies revealed that the intrinsic clearance of diflunisal, i.e., the ability of enzyme system(s) to metabolize the drug, was decreased in uremia. Also, plasma protein binding of diflunisal was decreased, which may explain the increase in apparent volume of distribution in uremic rats. The decreased intrinsic clearance of diflunisal in uremic rats may be due partly to saturation of biotransformation process(es) by increasing unbound concentration as a consequence of impairment of plasma protein binding of diflunisal, and partly due to the diminished enzyme activity of glucuronidation by renal failure. The lack of an effect of the esterase inhibitor phenylmethylsulfonyl fluoride on the intrinsic clearance of diflunisal in uremic rats suggested that the reduced intrinsic clearance of diflunisal was not attributable to the systemic enzymatic hydrolysis of the ester glucuronide.

Topics: Animals; Blood Proteins; Diflunisal; Glucuronates; Kinetics; Male; Metabolic Clearance Rate; Protein Binding; Rats; Rats, Inbred Strains; Salicylates; Uremia

Decreased binding of aromatic acidic drugs and endogenous metabolites to plasma proteins of patients with severe renal failure appears to be due to accumulation of unknown solutes. Both the warfarin and indole binding sites of albumin, the principal binding protein for these ligands, are affected. We used a large number of endogenous aromatic acids and synthetic congeners as displacers (a) better to characterize the chemical requirements for binding to each site and (b) to derive clues to the chemical structure of the undefined binding inhibitors in uremic plasma. 14C-tryptophan, 14C-warfarin and 14C-salicylate were used as bound ligands. Numerous indoles, quinolines and phenyl derivatives were moderate to strong displacers with several structural correlates. Increasing apolar side chain length enhanced displacing potency. A hydroxyl group at the 5 position of indoles and at the para position of phenyl derivatives severely reduced activity. The two ends of amphophilic molecules showed opposite requirements for displacement of tryptophan: the greater the polarity at the hydrophilic end, the greater the tryptophan displacing potency. Conversely, the greater the total hydrophobic mass of the remainder of the molecule, the more potent the inhibition of binding. The dipeptides l-tryptophyl-l-tryptophan and l-tryptophyl-l-phenylalanine were potent displacers. Computer-assisted analysis of warfarin binding in the presence of xanthurenic acid revealed inhibition by a mechanism other than simple competition, probably via a third albumin binding locus. We conclude that decreased binding in uremic plasma is most likely the summation effect of a number of retained aromatic acids, peptides, or both types of ligands.

Topics: Amino Acids; Blood Proteins; Hippurates; Humans; Indoles; Kynurenic Acid; Protein Binding; Quinolines; Salicylates; Salicylic Acid; Serum Albumin; Structure-Activity Relationship; Tryptophan; Uremia; Warfarin; Xanthurenates

We previously reported that an extract of uremic plasma reduces binding of phenytoin and tryptophan by normal plasma and plasma albumin. This effect appears to reproduce the impaired binding of many drugs and several endogenous metabolites by uremic plasma. In the present study we further characterized the properties of extracts from uremic sera and body fluids using binding of salicylate as a model. Salicylate was chosen because it binds to both of the main albumin binding loci for aromatic, acidic drugs. Using a computer-assisted, least-squares, curve-fitting program, LIGAND, we found that the most satisfactory model for salicylate binding to 1:10 diluted normal plasma was a binding number (n) of 2 mol of salicylate per mole of albumin with an association constant (k) of 2.85 X 10(4) L/mol, an additional binding of 0.5 mol to other sites on albumin or to other proteins, and nonspecific binding of 21%. Addition of uremic pleural fluid extract to diluted normal plasma produced a monotonic decline in k to 0.17 X 10(4) L/mol with no change in n except possibly at the highest dose of uremic inhibitor. This pattern of competitive inhibition indicates presence of unknown ligands in the uremic extract that compete at both binding loci. More efficient extraction methods might also yield additional ligand(s) that inhibit through a noncompetitive mechanism.

Topics: Adult; Aged; Binding, Competitive; Body Fluids; Humans; Ligands; Middle Aged; Salicylates; Salicylic Acid; Serum Albumin; Uremia

Carbamoylation of bovine and human albumin in vitro decreased the binding of methyl red and salicylic acid. Charcoal extraction of the carbamoylated albumin under acid conditions produced some decrease in the degree of carbamoylation, but did not substantially improve the binding of methyl red and salicylate. Albumin from rats with glycerol-induced renal failure showed no significant degree of carbamoylation compared to controls. Carbamoylation is not responsible for the binding defect of uraemic rat plasma, nor is likely to be involved in the case of human uraemic plasma.

Topics: Animals; Azo Compounds; Carbamates; Cattle; Humans; Pharmaceutical Preparations; Protein Binding; Salicylates; Salicylic Acid; Serum Albumin; Serum Albumin, Bovine; Uremia

Serum protein binding of weakly acidic drugs is impaired in uremia, but that of basic drugs tends to be normal. Treatment of uremic serum with anion exchange resin (Amberlite CG-400, acetate form) corrected binding defects for three acidic drugs (nafcillin, salicylate and sulfamethoxazole) but did not affect the binding of two basic drugs (trimethoprim and quinidine). Resin treatment of normal human serum did not alter the binding of these five drugs. Extraction of the acetate buffer eluate from resin exposed to uremic serum with n-butyl chloride at acidic pH (3.0) resulted in a fraction that could induce similar binding defects in normal human serum. The factor(s) responsible for binding defects in uremia appears to be lipid soluble, weakly acidic, and dialyzable. It is believed to be tightly bound to albumin at physiologic pH, but dissociates from it at acidic pH. These findings further support the previously proposed hypothesis that drug-binding defects in uremia are due to accumulation of certain endogenous metabolic product(s).

Topics: Adult; Aged; Anion Exchange Resins; Blood Proteins; Dialysis; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Nafcillin; Protein Binding; Quinidine; Salicylates; Serum Albumin; Sulfamethoxazole; Trimethoprim; Uremia

All patients in stupor or coma should undergo blood chemistry studies, including blood gases. The anion gap and serum osmolality must be calculated in all patients. An indwelling catheter to monitor urine content and volume is essential. Electrocardiogram monitoring is indicated in all significant metabolic acidosis, especially for evaluation of intracellular potassium effect and arrhythmias. Repeated arterial monitoring of blood gases and electrolytes is essential with the use of flow sheets. Sodium lactate and Ringer's solution should never be given in an emergency care area. Large doses of insulin (100+ units intravenously) are not necessary or indicated in diabetic ketoacidosis and may be contraindicated and dangerous especially in HHNKC. Intravenous or intramuscular regular insulin after urine tests for glucose and ketones alone should not be given. Urine dilution of serum ketones is useless, and serum dilution may be grossly misleading and contraindicated: arterial studies are much more reliable.

Topics: Acidosis; Blood Glucose; Diabetic Ketoacidosis; Diagnosis, Differential; Electrolytes; Emergencies; Ethylene Glycols; Humans; Hypoglycemia; Lactates; Metabolic Diseases; Methanol; Salicylates; Uremia

The effects of in vitro carbamylation of plasma with potassium cyanate on drug-protein binding have been investigated. Potassium cyanate added to samples of normal plasma and incubated for 30 to 150 min induced time-related plasma protein carbamylation. Carbamylation of plasma did not influence quinidine protein binding, but resulted in decreased salicylate binding. The increased free fraction of salicylate in plasma correlated with the degree of carbamylation of plasma proteins (r = 0.99; p less than 0.001). Plasma from patients with chronic renal disease showed varying degrees of plasma protein carbamylation, correlating with the values of free plasma salicylate (r = 0.80; p less than 0.05). Scatchard plots for sulfadiazine binding in plasma from patients with uremia and in normal plasma carbamylated in vitro with potassium cyanate showed changes in the 2 groups when compared with those in normal individuals. If cyanate is produced in vivo from urea in patients with uremia, plasma protein carbamylation may play a role in the decreased plasma protein binding of some acidic drugs.

Topics: Adult; Binding Sites; Binding, Competitive; Blood Proteins; Carbamates; Charcoal; Cyanates; Female; Humans; In Vitro Techniques; Kinetics; Male; Protein Binding; Salicylates; Serum Albumin; Sulfadiazine; Time Factors; Urea; Uremia

Diflunisal protein binding was studied by equilibrium dialysis at 37 degrees in plasma from healthy, uremic, and geriatric subjects. Binding data were computer analyzed assuming 2 classes of independent binding sites (Scatchard model). K1, the primary association constant for the diflunisal-albumin interaction, was substantially lower in uremic plasma (2.39 +/- 0.29 x 10(5) M-1) than in normal plasma (6.86 +/- 0.59 x 10(5) M-1). No difference was found between the number of primary diflunisal binding sites (N1) in uremic and normal plasma. In geriatric plasma neither K1 nor N1 differed from the normal values, indicating that decreased diflunisal plasma protein binding in the elderly is a result of lower plasma albumin concentration. Binding studies with plasma from uremic patients during hemodialysis revealed that free diflunisal rose from 0.46 +/- 0.04% at the start to 0.61 +/- 0.06% at the end of dialysis. Plasma free fatty acid concentrations rose similarly. In vitro displacement studies showed that oleic acid is a competitive inhibitor for the binding of diflunisal to human serum albumin. This may explain the decrease in diflunisal plasma binding at the end of hemodialysis treatment.

Topics: Adult; Age Factors; Aged; Binding Sites; Blood Proteins; Diflunisal; Heparin; Humans; Kidney Failure, Chronic; Kinetics; Middle Aged; Protein Binding; Renal Dialysis; Salicylates; Uremia

A quick simple method for emergency acetaminophen estimation is that of Glynn and Kendall (1975). Apart from the known interference of salicylate, sera from uremic patients was shown to give falsely high results. A modified method is presented, with a scanning check to identify the presence of such non-specific chromogens.

Topics: Acetaminophen; Blood Urea Nitrogen; Humans; Salicylates; Time Factors; Uremia

Topics: Adolescent; Anorexia Nervosa; Child, Preschool; Diagnosis; Diagnosis, Differential; Dysautonomia, Familial; Female; Glomerular Filtration Rate; Humans; Infant; Intellectual Disability; Intestinal Polyps; Male; Osteoma; Ovarian Neoplasms; Poisoning; Salicylates; Sarcoma; Testicular Neoplasms; Uremia; Uterine Cervical Neoplasms; Vaginal Neoplasms; Wilms Tumor

Protein binding of salicylate was studied by equilibrium dialysis at 37 degrees C in plasma from uremic patients and healthy subjects. The protein binding was considerably lower in the uremic plasma at all salicylate concentrations studied (14 to 1,400 mug/ml). Scatchard plots of the data were computer-analyzed assuming binding to the classes of binding sites. According to this analysis, the binding to the class of primary binding sites was considerably decreased in the uremic plasma. In addition to the effect of the uremic state, the binding was considerably decreased at high therapeutic plasma levels and at low albumin levels. The combined effect of two or three of these factors may lead to unexpectedly high unbound fractions of salicylate, which should be considered in the monitoring of plasma salicylate levels in patients.

Topics: Adult; Aged; Binding Sites; Blood Proteins; Computers; Female; Humans; Male; Middle Aged; Protein Binding; Salicylates; Uremia

Protein binding of numerous drugs, primarily organic acids, is decreased in sera from uremic patients. The defect in binding is (1) greater than can be accounted for by hypoalbuminemia alone; (2) unchanged by prolonged in vitro dialysis; (3) transferred in the protein but not the ultrafiltrate fraction of uremic serum; and (4) not reproduced by addition of low and middle molecular weight compounds known to accumulate in uremia. However, treatment with activated charcoal at pH3 was found to significantly increase drug protein binding in uremic sera. This effect was studied with six different drugs in sera from groups of 6 normal subjects and 8 patients on chronic hemodialysis. The percentage of sulfamethoxazole, dicloxacillin, diphenylhydantoin, salicylate, and digitoxin bound to protein in normal sera (65.9, 97.1, 93.1, 96.7, and 92.7, respectively) was unchanged by charcoal treatment. In contrast, charcoal treatment significantly (p less than 0.01) increased the percentage of drug bound to protein in uremic sera from 41.7 to 59.0 for sulfamethoxazole, 90.7 to 96.3 for dicloxacillin, 84.3 to 90.8 for diphenyhydantoin, 86.4 to 93.8 for salicylate, and 89.5 to 90.9 for digitoxin. Charcoal treatment significantly (p less than 0.05) reduced penicillin protein binding in normal sera and failed to correct the binding defect for penicillin in uremic sera. The effect of charcoal can be explained by removal of an inhibitor which accumulates in uremia and (1) occupies the binding site of certain drugs, (2) changes the configuration of the albumin molecule, or (3) both. Free fatty acid (FFA) concentrations in uremic patients were similar to those in normal subjects and were not the cause of the binding defect.

Topics: Blood Proteins; Charcoal; Dicloxacillin; Digitoxin; Fatty Acids, Nonesterified; Humans; In Vitro Techniques; Penicillin G; Phenytoin; Protein Binding; Renal Dialysis; Salicylates; Serum Albumin; Sulfamethoxazole; Uremia

The plasma protein binding of phenytoin (DPH) was studied by equilibrium dialysis at 37 degrees C in plasma from uremic patients and healthy subjects. Scatchard plot analyses demonstrated a decreased association constant Ka for the DPH-albumin interaction in the uremic plasma (mean 1.76 - 10(3) M-1 +/-SD 0.12 and a mean 4.10 - 10(3) M-1 +/- SD 0.24 in normal plasma). Studies on separated fractions of serum did not indicate any significant binding of DPH to proteins other than albumin. The nonlinear mathematical relationship between bound DPH and serum albumin could be linearized at low drug concentrations by plotting the ratio of bound/unbound DPH against albumin concentration. The displacement effect of salicylic acid at a concentration of 276 mug/ml (2mM) and DPH was considerable in plasma from normal subjects. In uremic plasma the effect was of much smaller magnitude.

Topics: Adult; Aged; Binding, Competitive; Blood Proteins; Female; Humans; Kinetics; Male; Middle Aged; Phenytoin; Protein Binding; Salicylates; Serum Albumin; Uremia

Topics: Blood Proteins; Humans; Kinetics; Protein Binding; Salicylates; Tubocurarine; Uremia

Two and three Dow Cordis Hollow Fiber and Gambro Lundia artificial kidneys were used for high efficiency dialysis in large patients, intoxications, and for rapid ultrafiltration. BUN clearances of up to 240 ml/min were achieved. One episode of severe neuropathy occurred during high efficiency dialysis, and hypotensive episodes were more common. High efficiency dialysis has certain indications particularly in intoxication cases. However, because of possible side effects more experience is needed before its ultimate place in the treatment of uremia can be ascertained.

Topics: Barbiturates; Blood Urea Nitrogen; Body Weight; Calcium; Creatinine; Edema; Headache; Humans; Hypotension; Kidneys, Artificial; Nausea; Phenobarbital; Phenytoin; Poisoning; Primidone; Renal Dialysis; Salicylates; Substance-Related Disorders; Ultrafiltration; Uremia; Uric Acid

Topics: Anemia; Animals; Cattle; Dihydroxyphenylalanine; Dogs; Down Syndrome; Fever; Glycine; Humans; Hypertension; Liver Diseases; Methyldopa; Mitochondria, Liver; Pheochromocytoma; Rats; Salicylates; Swine; Uremia; Wounds and Injuries

Topics: Blood; Blood Proteins; Epilepsy; Epilepsy, Tonic-Clonic; Female; Humans; Hyperbilirubinemia; In Vitro Techniques; Infant; Infant, Newborn; Infant, Newborn, Diseases; Male; Phenytoin; Protein Binding; Salicylates; Serum Albumin; Umbilical Cord; Uremia

Topics: Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelet Disorders; Blood Protein Disorders; Humans; Kidney Failure, Chronic; Leukemia; Liver Diseases; Salicylates; Thrombocythemia, Essential; Uremia

Topics: Adolescent; Anemia; Anemia, Macrocytic; Anemia, Megaloblastic; Colchicine; Genetics, Medical; Gout; Intestinal Diseases; Intestinal Obstruction; Intestine, Small; Kidney Diseases; Pathology; Salicylates; Substance Withdrawal Syndrome; Substance-Related Disorders; Toxicology; Uremia; Uricosuric Agents

Topics: Acidosis; Acute Kidney Injury; Alcoholism; Anuria; Child; Diabetes Mellitus; Dialysis; Humans; Hypertension; Hypertension, Malignant; Hyponatremia; Malaria; Peritoneal Dialysis; Poisoning; Renal Dialysis; Renal Insufficiency; Salicylates; Uremia

Topics: Blood Chemical Analysis; Blood Glucose; Blood Platelets; Calcium; Charcoal; Creatine; Creatinine; Glomerulonephritis; Humans; Kidney; Kidneys, Artificial; Perfusion; Polycystic Kidney Diseases; Salicylates; Urea; Uremia; Uric Acid

Topics: Biological Transport; Body Fluids; Humans; Salicylates; Uremia; Urine; Urologic Diseases