Biomedical subjects

A W Pruitt

Publications and source records attributed to A W Pruitt.

At least 37 records · Page 2Linked to original sources

PubMed1977

Depression of renal clearance of furosemide in man by azotemia.

The renal clearance of furosemide and tetraethylammonium (TEA) were compared in 10 patients with hypertensive nephropathy. BUN and creatinine ranges were 10 to 88 mg/dl and 0.9 to 3.8 mg/dl, respectively. Diuretics were discontinued 48 hr prior to the study, and 2 consecutive clearances (ml/min/1.73 m2BSA) of creatinine were performed. The patient then received a bolus followed by a constant infusion of furosemide-14C and tetraethylammonium-14C (analyzed by specific methodology for plasma and urine), both in subpharmacologic doses. After 40-min equilibration sequential 20-min clearance periods were obtained. Both the clearance of furosemide (range 17 to 133) and TEA (range 99 to 443) correlated negatively with BUN and serum creatinine and positively with creatinine and urea clearances. Thus, by using a constant-infusion technique we demonstrated that the renal clearance of furosemide is depressed by azotemia in man and that there was greater depression with furosemide than with TEA.

Adult↗

PubMed1977

Variations in the fate of triameterene.

Triamterene is a pteridine used therapeutically as a diuretic. In order to better understand variations in effect and toxicity of triamterence in individuals, the fate of the drug in man was investigated. Both nonradioactive and 14C-labeled forms of the drug were administered, and specific methods of analysis were used to separate the parent compound from its metabolite. Individual variation in absorption, binding, and elimination was noted. The drug was excreted in bile as well as urine. Rapid and extensive metabolism of the agent occurred after oral and intravenous doses in healthy adult men. The peak plasma levels of the drug after an oral dose (200 mg) were under 0.3 microng/ml, but the concentration of the primary metabolite. (2,4,7-triamino-6-p-hydroxyphenylpteridine) was higher. The urinary excretion of the metabolite was at least three times that of the parent drug.

Administration, Oral↗

PubMed1977

Spectrophotofluorometric assay for isoniazid and acetyl isoniazid in plasma adapted to pediatric studies.

We modified the micro-scale spectrophotofluorometric method of Miceli et al. [Biochem. Med. 12, 348 (1975)] for the assay of "apparent" isoniazid (isoniazid acid-lable hydrazones) to improve its clinical application. We also adapted the method for determination of acetyl isoniazid. Data are presented showing how long plasma containing isoniazid may validly be stored. The applicability of the method was demonstrated in studies on children and small animals.

Adolescent↗

PubMed1977

The measurement of 3-o-methyldopamine in urine and plasma by a rapid and specific radioimmunoassay.

Antiserum against 3-O-methyldopamine (MD) was produced in rabbits immunized with MD hapten conjugated to hemocyanin. The antiserum was used to develop a radioimmunoassay (RIA) for MD. As little as 0.5 ng of MD in 0.1 ml can be detected. The major catecholamines and the phenolic aromatic amines (dopamine, norepinephrine, epinephrine, octopamine, and tyramine) and their metabolites (normetanephrine, metanephrine, homovanillic acid and 4-hydroxy-3-methxymandelic acid) did not bind significantly to the antibody. The RIA of MD was used to assay the endogenous level of MD in urine and plasma of hospitalized children. In children (7 mo to 13 yr), average concentration of MD in plasma was found to be 0.47 +/- 0.11 ng/ml, and in urine 0.15 +/- 0.05 microgram/mg of creatinine (45.0 +/- 16.3 microgram/24 hr). In children with neuroblastoma, there was a 3- to 10-fold increase in urinary excretion and plasma level of 3-O-methyldopamine. In adults, the average urine and plasma levels were found to be 87.4 +/- 3.4 microgram/24 hr and 0.6 +/- 0.2 ng/ml. The diagnostic applicability of the RIA of MD is discussed.

Adolescent↗

PubMed1976

Hypertension, hyperreninemia and a solitary renal cyst in an adolescent.

Solitary renal cysts associated with hypertension and documented hyperreninemia are relatively uncommon. A 13 year old boy with these findings is described (pressure 160/120 mm Hg). Contrast studies of the urinary tract and arteriography with selective renal vein sampling demonstrated a solitary cyst in the right kidney. The ratio of plasma renin activity in the right renal vein to left renal vein (RRV:LRV) was 2.35:1. After drainage of the cyst, there was a marked reduction in both systolic and diastolic pressures (126/84 mm Hg). Hypertension has not recurred during 14 months' follow-up.

Adolescent↗

PubMed1976

Diuretic effect of furosemide in acute glomerulonephritis.

Twenty-five children with the diagnosis of acute glomerulonephritis were treated with oral or intravenous doses of furosemide. The intravenous administration of 1 mg/kg or greater resulted in an increase in urine volume in all patients. Oral doses of less than 2 mg/kg were not as effective, but there was wide variation in diuretic response to the drug. In 13 patients, plasma concentrations of furosemide were measured. The plasma half-life varied from 2.3 to 4.4 hours after intravenous administration of the drug. The plasma concentration of furosemide did not correlate with diuretic response.

Acute Disease↗

PubMed1976

Effect of experimental azotemia on renal clearance of furosemide in the dog.

The clearance of furosemide (F), whose renal tubular transport shares the classical characteristics of the organic acid system, was determined in dogs with varying degrees of azotemia and compared with tetraethylammonium (TEA), an organic base. Two normal and eight azotemic dogs [blood urea nitrogen (BUN), 12-273] were studied. Azotemia was produced by bilateral uretero-venous anastomoses. The left renal vein and ureter were cannulated and renal blood flow (RBF) was measured by electromagnetic flowmeter. Simultaneous left renal clearances (C) of subpharmacological doses of TEA-14C and furosemide-14C were determined at seven 30-minute intervals. Initial loading doses were followed by continuous maintenance infusions. For TEA, clearance (1.5 ml/min-g +/- 0.2 S.E.M.) and extraction (E) (0.83 +/- 0.02) are independent of the degree of azotemia. Renal plasma flow (RPF), calculated as CTEA/ETEA, agreed closely with directly measured RPF (2.0 ml/g-min +/- 0.3). RPF was independent of azotemia. To allow for individual differences in the animals in RPF, the ratio CTEA/CF was used. CF (1.07-0.17 ml/min-g) and EF (0.54-0.06) decreased as a linear function of the increase in uremic serum: (see article). Furosemide and its principle metabolite were greater than or equal to 97% of the furosemide portion of the radioactivity. The metabolite did not increase with time in either plasma or urine. After acute administration of exogenous urea to two dogs (BUN 170 and 253) CTEA/CF was unrelated to BUN. Thus, the CF decreases proportionately with progressive azotemia and is not related to RBF, exogenous urea or metabolite. This suppression of renal tubular secretion of furosemide may partially account for reduced therapeutic efficacy of furosemide in azotemia.

Animals↗

PubMed1976

Relationship of urinary furosemide excretion rate to natriuretic effect in experimental azotemia.

The relationship of natriuretic effect and furosemide excretion was studied in normal and azotemic dogs. Graded azotemia was produced in dogs by bilateral uretero-venous shunts of varying duration. The shunts were subsequently opened and urine and blood samples were taken to measure inulin, furosemide and sodium concentrations. Renal blood flow was measured by an electromagnetic flow probe. Two groups of dogs, control and experimental, were studied. The experimental group received a loading dose followed by a constant infusion of furosemide. This dose produced a natriuresis in nonazotemic normal dogs. The magnitude of this natriuresis correlated with furosemide excretion rate (P less than .005) and not with the plasma concentration of the drug. Furosemide clearance and extraction were inversely correlated with blood urea nitrogen. In the furosemide-treated group the augmentation of sodium excretion was not impaired except at blood urea nitrogen concentrations of greater than 200 mg/dl (two dogs). Thus the reduced clearance of furosemide may account in part for the high dose necessary. Further studies appear to be in order to clarify the relationship of the natriuretic response to furosemide to the rate of urinary excretion and plasma concentration of the drug.

Animals↗

PubMed1975

Furosemide binding to human albumin and plasma of nephrotic children.

The extent and nature of furosemide (F) binding to human albumin (HA) and to the plasma of 6 children with nephrotic syndrome were studied by equilibrium dialysis at 37 degrees C and pH 7.4 with 14C-F. At a total concentration of 3.4 mug/ml (therapeutic range), the unbound fraction of F to 4 gm per 100 ml HA was 2.79 plus or minus 0.35. The degree of binding was relatively constant from 1.8 to 36 mug/ml of F concentration. The percentage of unbound F doubled when total concentration of the drug was increased more than 130 times (1.8 to 245 mug/ml). F has two classes of binding sites (n1 = 1.42, k1 = 5.07 times 10-4 M-minus 1; n2 = 3.4, k2 = 1.58 times 10-4 M-minus 1); interaction with HA involves hydrophobic, ionic, and hydrogen forces. Acetylsalicylic acid (ASA), acetazolamide, diazoxide, phenylbutazone, sulfisoxazole (S), and tolbutamide (T) decreased F binding. Combinations of ASA, S, and T exerted a strong additive displacing effect. The binding of the F metabolite (4-chloro-5-sulfamoylanthranilic acid, CSA) was studied at 1.3 and 2.6 mug/ml. The unbound fraction was 5 times that of F. CSA did not influence F binding. Studies with plasma of 7 healthy adults showed that albumin is the only plasma protein responsible for F binding. The plasma albumin concentration range of the children with nephrotic syndrome was 0.6 to 2.1 gm per 100 ml. There was some correlation between albumin concentration and binding of F (2.8 to 9.6% unbound); this corresponded with findings with HA. Albumin concentrations lower than 2 gm per 100 ml seemed to influence the extent of the unbound fraction of F considerably.

Acetazolamide↗

PubMed1975

A complex pattern of disposition of phenytoin in severe intoxication.

A 5-year-old child developed phenytoin (diphenylhydantoin, DPH) toxicity after receiving 500 mg of the drug daily for 3 weeks. Plasma, urine, and duodenal fluid were collected for assay of DPH and its metabolites. The peak plasma concentration of DPH was 108 mug/ml, and the decline in plasma level did not fit first-order kinetics. The para-hydroxy, meta-hydroxy, and dihydrodiol metabolites of DPH were measured in urine; duodenal aspirate contained both DPH and the para-hydroxy metabolite. Plasma pH may affect distribution of DPH since in vitro binding of DPH to human albumin increased as pH increased.

Child, Preschool↗

PubMed1974