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Biomedical subjects

S Jacobsen

Publications and source records attributed to S Jacobsen.

At least 127 records · Page 7Linked to original sources
PubMed1983

Binding of theophylline in human serum determined by ultrafiltration and equilibrium dialysis.

1 Binding of theophylline (80 mumol/l) was determined in serum from healthy subjects by equilibrium dialysis and by ultrafiltration, using [3H]-theophylline, at 22 degrees C and at different pH-values. pH was regulated by gassing with CO2 or by dialysing the serum against a phosphate buffer before use. 2 Binding of theophylline in serum was 34-38% determined by equilibrium dialysis and 41-45% determined by ultrafiltration at pH 7.4-7.5. The protein concentration in serum decreased by 12-16% during equilibrium dialysis and increased by 20% during ultrafiltration. The intersubject variation in binding was small. 3 Binding of theophylline in serum was pH-dependent with 25-30% bound at pH 7.0 and 58-60% bound at pH 8.1-8.3. Binding was significantly correlated to the fraction of ionized theophylline. 4 The binding of theophylline in normal human serum is about 35-40% at pH 7.4 and 22 degrees C. The difference in binding observed between equilibrium dialysis and ultrafiltration may be explained by the opposite changes in protein concentration during the experiment. 5 Control of pH is necessary to obtain physiologically relevant data on drug binding in serum.

Adolescent↗
PubMed1983

Lack of hyperglycemic effect of chlorothiazide in normal rats fed diets with different carbohydrate content.

The effect of chlorothiazide (CT) on blood glucose and liver glycogen was investigated in rats fed either a standard, a carbohydrate-rich, or a carbohydrate-poor diet. CT did not alter blood glucose concentration or liver glycogen content in rats fed the carbohydrate-rich diet. After 5 days on the carbohydrate-poor diet, an oral glucose load produced significantly smaller rate constant for glucose disappearance from blood and significantly greater area below the glucose concentration--time curve than after a standard diet, but CT did not further alter these parameters. Nor did oral CT for 19 days alter glucose tolerance. In conclusion, CT in single dose or short term studies does not seem to alter glucose metabolism in the normal male rat.

Animals↗
PubMed1982

Interaction of hydroflumethiazide and 2,4-disulfamyl-5-trifluoromethylaniline with cyclic AMP phosphodiesterase and carbonic anhydrase.

The inhibitory effect of hydroflumethiazide (HFT) and its metabolite, 2,4-disulfamyl-5-trifluoromethylaniline (DTA) on cyclic AMP phosphodiesterase and the binding of HFT and DTA to carbonic anhydrase was studied in vitro. Significant inhibition of rat kidney low-Km cyclic AMP phosphodiesterase was observed with DTA concentration above 2.5 X 10(-4) mol/l and with HFT concentration above 1 X 10(-4) mol/l. 50% inhibition was observed at a DTA concentration of 1 X 10(-3) mol/l. Binding of DTA and HFT to commercially obtained bovine erythrocyte carbonic anhydrase was demonstrated by equilibrium dialysis. Data were consistent with one class of binding sites. The product of n (number of binding sites) and Kass (association constant) was 5 X 10(5) M for DTA and 3.3 X 10(4) M for HFT at 2 degrees. In human blood in vitro at 37 degrees, the equilibrium erythrocyte/plasma concentration ratio was 18 for DTA and 1.6 for HFT. It is concluded that HFT and DTA have approximately the same potency as cyclic AMP phosphodiesterase inhibitors, whereas DTA is more extensively bound by erythrocyte carbonic anhydrase.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1981

Effect of urine pH and flow on renal clearance of methotrexate.

Hydration and urinary alkalinization are used with high doses of methotrexate (MTX) to prevent precipitation of the drug in the renal tubules and consequential nephrotoxicity. The quantitative effect of these measures on the renal clearance of MTX was studied in 8 patients with normal renal function, and in 3 patients with reduced renal function. Multiple regression analysis indicated an influence of both factors on the ratio of the renal clearances of MTX and creatinine. In the eleven patients there was a linear correlation between this ratio and urine pH (p less than 0.001); the ratio increased from 0.88 at pH 5.5 to 2.62 at pH 8.4. The pH effect on this ratio was similar in the patients with normal and reduced kidney function. An increase in urine flow did not significantly increase the ratio between renal clearance of MTX and creatinine. The effect of urinary alkalinization on renal MTX clearance could be clinically exploited in patients with delayed elimination of MTX. The probable modifying effect of alkalinization of urine on the intentionally high plasma concentration after high dose MTX infusions should be further evaluated, particularly in patients with normal renal function.

Adolescent↗
PubMed1981

Effects of hydroflumethiazide in congestive heart failure: renal electrolyte excretion related to urinary thiazide excretion and aldosterone.

The effect of hydroflumethiazide (HFT) on renal excretion of sodium, chloride, and potassium was studied in congestive heart failure and related to urinary excretion of thiazide and aldosterone. HFT 75 or 150 mg was administered orally once daily for 4 days to 8 male patients with roentgenological evidence of enlarged heart and slight or no peripheral oedema receiving digitalis and controlled diet. Urinary excretion of HFT did not change after repeated doses, whereas urinary excretion of a metabolite increased significantly. Initially, HFT induced a significant increase in the urinary excretion of sodium and potassium. After repeated doses, the natriuretic effect declined gradually in 6 of the patients. There was consistently a small natriuretic effect and a large kaliuretic effect at high serum aldosterone concentrations and high urine aldosterone excretion rates, whereas at low aldosterone levels, there was a wide range in magnitude of these effects. Relationships of the log urinary excretion rate of HFT to the increase in urinary excretion rate of sodium, chloride, and potassium showed positive and significant correlations. It was concluded that reduced natriuretic effect of HFT in congestive heart failure is not due to reduced delivery of thiazide to renal tubular cells but to compensatory adjustments of the kidney in part induced by aldosterone.

Aged↗
PubMed1981

Effect of repeated doses of hydroflumethiazide on renal excretion of electrolytes and uric acid in healthy subjects.

Urinary excretion of electrolytes and uric acid was investigated in six healthy subjects during repeated oral administration of 100 mg hydroflumethiazide (HFT) daily for seven days, and related to urinary thiazide excretion. Mean 24 hr-urinary excretion of sodium and chloride increased 100% (P less than 0.02) after the first HFT-dose, whereas 24 hr-excretion values were at control level after the fourth and seventh doses. Mean 24 hr-urinary excretion of potassium was increased by 31% after the first HFT-dose (P less than 0.05) and by 47% after the fourth dose (P less than 0.05). After HFT was discontinued, mean urinary excretion rates of sodium and chloride dropped to 30% and that of potassium to 70% of control. In the state of fluid deficiency and elevated aldosterone concentration, there was a significant positive correlation between log excretion rate of HFT and excretion rate of sodium (r=0.68, P less than 0.002) calculated from excretion data 0-67, 6-12, and 12-14 hrs after the seventh dose. After the first dose of HFT, sodium excretion was also significantly correlated to log excretion rate of HFT (r=0.86, P less than 0.001) but was probably influenced by other factors as well. Mean serum concentration of uric acid increased significantly, but mean 24 hr-urinary excretion of uric acid was constant during HFT-treatment.

Adult↗
PubMed1980

Pharmacokinetics and saluretic effect of muzolimine in severe cardiac failure.

Pharmacokinetics and effects on renal electrolyte excretion of a new diuretic drug, muzolimine (Bay g 2821), were investigated in 6 patients with severe congestive cardiac failure (New York Association classification Groups III and IV). After a single oral dose of 30 mg muzolimine, mean urinary excretion rate of sodium increased from 1.37 to 4.30 mmol/hour during the initial 24 hours, that of chloride from 0.86 to 3.97 mmol/hour, that of potassium from 1.23 to 1.63 mmol/hour, and that of water from 25.8 to 49.9 ml/hour. The saluretic effect lasted for 10 to 14 hours in 1 patient, 14 to 24 hours in 2, and more than 24 hours in 3 patients. Peak plasma concentrations of muzolimine occurred 1 to 7 hours after administration and averaged 487 ng/ml (range 268 to 868). Mean biological half-life of muzolimine in plasma was 14.3 hours (range 9.0 to 21.2 hours). The saluretic effect of muzolimine in congestive cardiac failure, thus, is of long duration, which may be explained by its long biological half-life.

Aged↗
PubMed1979

Excretion of hydroflumethiazide in bile and urine of man.

Biliary and urinary excretion of hydroflumethiazide (HFT) and its metabolite, 2,4-disulfamyl-5-trifluoromethylaniline (DTA), was investigated in 5 otherwise healthy patients with a T-drain in the common bile duct after cholecystectomy and choledochotomy. After a single oral dose of HFT 302--453 micromoles, a mean of 0.051% (range 0.028--0.075) of the dose was excreted in bile and 34.9% (range 23.7--45.4) in urine during the first 6 hours after administration. Biliary excretion appeared to be of minor importance in the elimination of HFT by man. DTA could not be detected in bile.

Adult↗
PubMed1979

Pharmacokinetics of quinidine related to plasma protein binding in man.

The disposition and plasma protein binding of quinidine after intravenous administration were studied in 13 healthy subjects. Plasma protein binding, expressed as the fraction of quinidine unbound ranged from 0.134--0.303 (mean 0.221). Elimination rate constant (beta) varied from 0.071 to 0.146 h-1 (mean 0.113), and apparent volume of distribution (Vbeta) varied from 1.39--3.20 1 . kg-1 beta (mean 2.27). Total body clearance was 2.32--6.49 ml min-1 . kg-1. There was a positive linear correlation between the plasma fraction of unbound quinidine and both V beta (r = 0.885, p less than 0.01) and total body clearance (r = 0.668, p less than 0.05). No significant correlation existed between the fraction of unbound quinidine in plasma and the elimination rate constant. The results show that both the apparent volume of distribution and total body clearance of quinidine are proportional to the unbound fraction in plasma. This implies that the total plasma concentration of quinidine at steady state will change with alterations in plasma binding, whilst the concentration of unbound compound and its elimination rate will remain unaffected.

Blood Proteins↗
PubMed1979

Pharmacokinetics of a single oral dose of muzolimine in cardiac failure.

The pharmacokinetics of a new "high ceiling" diuretic, muzolimine (Bay g 2821), were investigated after a single oral dose of 40 mg in 7 patients with cardiac failure (Stages I-IV, New York Heart Association classification), and in 2 healthy subjects. Plasma concentrations peaked 1-3 h after administration and declined according to a two-compartment model. The alpha-phase (distribution phase) lasted until 12-16 h after administration and the mean t 1/2 a was 3.6 h (range 2.3-4.7) in patients, and 2.6 h (range 2.3-2.9) in healthy subjects. The mean t 1/2 beta was 13.5 h (range 7.4-22.4) in the patients and 14.0 h (range 12.4-14.6) in healthy subjects. T 1/2 beta was not correlated with the degree of heart failure or with the area beneath the plasma concentration curve, which varied three-fold. The renal clearance of muzolimine was in the range 2.7-15.3 ml . min-1 in 5 subjects in whom it was investigated. The pharmacokinetics of muzolimine appear not to be significantly altered by cardiac failure. The prolonged half-lives of the drug are probably responsible for the longer duration of diuretic action reported for muzolimine than for furosemide and bumetamide.

Adult↗