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Biomedical subjects

U Gundert-Remy

Publications and source records attributed to U Gundert-Remy.

At least 37 records · Page 2Linked to original sources
PubMed1985

Integrated pharmacokinetics and pharmacodynamics of atropine in healthy humans. II: Pharmacodynamics.

This study determined the kinetics of the effects of atropine on heart rate and saliva flow in three healthy male volunteers after intravenous administration of 1.35 and 2.15 mg of the drug. The pharmacokinetics of atropine and its primary metabolite, tropine, were determined simultaneously. Both the pharmacokinetic and effect data were fitted to an integrated kinetic-dynamic model. The maximum heart rate and minimum saliva flow occurred with a significant delay of 7-8 min after drug administration. Both effects were nonlinearly related to the amount of drug in the peripheral compartment. Maximum heart rates of 192 and 217% of the control values were observed at the lower and higher dose levels, respectively. Minimum saliva flows of 8 and 3% of the control values were measured after the lower and higher doses of atropine, respectively. The time durations of the positive chronotropic effect of the drug were 170 and 250 min at the lower and higher dose levels, respectively; the corresponding values for the length of the antisialogogue effect of the drug were 230 and 340 min, respectively.

Absorption↗
PubMed1985

Pharmacokinetics of ceftizoxime.

The kinetics of ceftizoxime, a newly developed cephalosporin, were evaluated in 6 healthy subjects, with respect to its excretory pathways especially by the biliary route. Total, renal and biliary clearance were determined at two different steady states. Steady state was achieved by constant intravenous infusion (604.1 mg/h) over 6 h after an initial loading dose (750 mg); 1.5 h after discontinuation of that infusion, a further infusion was commenced at a lower rate (284 mg/h) over 3 h, the second steady state being reached 0.5 to 1.0 h later. The drug was mainly excreted by the kidneys (56.7 to 92.9% of the dose). Biliary excretion, measured by the duodenal perfusion and marker dilution technique, was low (0.2 to 7.8% of the dose). Urinary and biliary excretion as well as total clearance were not dose-dependent. However, there was pronounced interindividual variation in total (35.2 to 236 ml/min) and renal clearance (10.6 to 208 ml/min), which could both be explained by varying interindividual urinary flow rates (mean flow rate: 0.99 ml/min to 3.14 ml/min). Intraindividual variation in renal clearance was less pronounced, but in the same subject changes in renal clearance were correlated with changes in urinary flow rate. From the varying renal clearance, which exceeded the glomerular filtration rate at high urinary flow rates and was below it at low urinary flow rates, it can be concluded that, in addition to glomerular filtration, tubular secretion and tubular reabsorption are involved in the renal excretion of ceftizoxime.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Pharmacokinetics of sulphinpyrazone and its major metabolites after a single dose and during chronic treatment.

The pharmacokinetics of sulphinpyrazone and its major metabolites (sulfide, sulfone, p-hydroxysulfone and p-hydroxy-sulphinpyrazone) were investigated in 9 volunteers after a single oral dose as well as after chronic treatment for 23 days. Chronic administration of sulphinpyrazone, in comparison with a single oral dose, led to significant changes in plasma AUC (115.86 to 42.90 mg/l . h), in renal clearance (1.06 to 1.80 l/h), in hepatic intrinsic clearance (319.0 to 598.0 l/h), and in the unbound fraction in plasma 1.15 to 1.69%) and in tissue (2.73 to 1.31%). The volume of distribution changed from 20.24 to 52.04 l. The steady state concentrations predicted from the single dose were significantly higher than the values found after chronic treatment. The results suggest that sulphinpyrazone induces its own metabolism. The metabolism of the sulfone, p-hydroxysulfone and the p-hydroxy-sulphinpyrazone to further degradation products was also induced. Chronic treatment with sulphinpyrazone reduced the plasma AUC of the sulfide and caused a decrease in its elimination half-life (20.9 to 14.3 h). Since considerable amounts of the sulfide are formed in the G.I. tract, it is suggested that besides the induction of metabolism, bacteria which reduce sulphinpyrazone to the sulfide may also be responsible for the observed pharmacokinetic changes.

Adult↗
PubMed1983

Effect of single and multiple doses of sulphinpyrazone on antipyrine metabolism and urinary excretion of 6-beta-hydroxycortisol.

Sulphinpyrazone decreases the plasma clearance of tolbutamide and S-warfarin and increases the clearance of R-warfarin, theophylline and antipyrine. In order to determine whether sulphinpyrazone is an inducer or inhibitor or both of oxidative drug metabolism, antipyrine and its metabolites as well as 6-beta-hydroxycortisol were measured in urine before, 24 h and after 23 days of chronic administration of sulphinpyrazone (4 X 200 mg/day). During chronic treatment sulphinpyrazone increased the ratio of 6-beta-hydroxycortisol to the 17-hydroxycorticosteroids by 70% (p less than 0.02). The renal clearance of the main oxidative metabolites of antipyrine (4-hydroxyantipyrine, 3-hydroxymethylantipyrine and norantipyrine) were increased after sulphinpyrazone (p less than 0.02). Except for norantipyrine, no change in total excretion of antipyrine and its metabolites occurred after 24 h or after 23 days. It is concluded that sulphinpyrazone induces the enzymes which metabolize antipyrine and cortisol.

Adult↗
PubMed1983

Nonlinear mezlocillin kinetics due to dose-dependent metabolism.

Dose-dependent kinetics of intravenous bolus-dose mezlocillin, a newly developed ureidopenicillin, have been reported by several investigators. In eight healthy subjects we examined renal, biliary, and total clearance at different steady-state levels. After infusion of doses of 22.4 +/- 1.5, 11.4 +/- 0.7, and 5.6 +/- 0.4 mg/min mean plasma steady-state levels of 88.4 +/- 15.9, 40.3 +/- 7.5, and 18.4 +/- 4.6 micrograms/ml were achieved. Metabolic clearance was estimated as the difference between total clearance and the sum of renal and biliary clearance, assuming that no other route of excretion plays an important role in the elimination of the drug. Total clearance varied between 355.7 +/- 59.3 and 286.5 +/- 54.6 ml/min when doses of 5.6 +/- 0.4 and 22.4 +/- 1.5 mg/min were given. Since neither renal clearance (137.6 +/- 32.6 ml/min) nor biliary clearance (98.6 +/- 42.5 ml/min) was shown to be dose dependent, nonlinear mezlocillin kinetics must be due to dose dependent metabolic clearance (108.4 +/- 26.2 versus 60.2 +/- 32.3 ml/min at 5.6 +/- 0.4 and 22.4 +/- 1.5 mg/min). The apparent Km was 27.5 micrograms/ml and apparent Vmax 4.3 mg/min. The apparent Km is so low that after therapeutic doses of mezlocillin the kinetics are nonlinear for several hours.

Adult↗
PubMed1982

Estimation of biliary excretion of ureidopenicillins in healthy volunteers using marker dilution technique.

1 Aspiration of duodenal fluid and estimation of recovery by a marker dilution technique was adapted to measure the biliary excretion of two chemically related ureidopenicillins, mezlocillin and azlocillin, in healthy volunteers. 2 The drug was infused intravenously at a constant rate over a period of 6 h during which duodenal fluid was aspirated through the distal opening of a triple-lumen polyvinyl tube. 3 Drug levels in plasma, urine and duodenal fluid were determined by h.p.l.c. 4 Biliary excretion rate was calculated by multiplying the concentration in the duodenal fluid by the dilution factor resulting from the dilution of marker substance infused through the proximal opening of the triple-lumen tube. 5 Since the results obtained by the marker dilution technique are comparable to data obtained by studies in patients with t-tube drainage following biliary surgery, it can be concluded that the method is useful to measure the biliary excretion of drugs in man.

Adult↗
PubMed1981

[Degradation of Azlocillin and Mezlocillin / I. Behaviour in biological material and buffer (author's transl)].

The degradation of 6-[(R)-2-(2-oxo-imidazolidine-1-carboxamido)-2-phenyl-acetamido] penicillanic acid Na-salt (azlocillin, Securopen) and 6-[(R)-2-[3-methylsulfonyl-2-oxoimidazolidine-1-carboxamido]-2-phenyl-acetamido ] penicillanic acid Na-salt (mezlocillin, Baypen), two chemically related acylureido penicillins, was tested in biological material (plasma and urine) and borate buffer at 37 degrees C over the time period of at least 6 h. In fresh human urine (pH 5.0) no degradation could be observed. In freshly prepared human plasma (pH 7.6) degradation was independent of the initial concentration and amounted to no more than 5%. No difference could be noted between the degradation in plasma or buffer, respectively, indicating that direct aminolysis did not play an important role in the degradation process. The extent of degradation could be demonstrated to be pH-dependent. After 8 h incubation at pH 9.0 azlocillin concentration was decreased to 70% and mezlocillin concentration to 50%, respectively, of the initial concentration. Since urinary pH values up to 8.5 are reported the urinary recovery of the substance could be influenced by alkaline pH.

Azlocillin↗
PubMed1979

Plasma and urinary levels of triamterene and certain metabolites after oral administration to man.

The plasma and urinary levels of triamterene and two metabolites were measured using a specific method of analysis. Urinary excretion was completed after 48 h, which permitted a rough estimate of its half-life as longer than two hours. The areas under the curve were 672.5 +/- 160.3 and 1.311.3 +/- 399.1 micrograms/ml X h after the triamterene 150 mg and 300 mg p.o., respectively and correspondingly 4.2 +/- 1.4% and 3.7 +/- 0.6% of the dose were excreted as unchanged drug. The principal metabolite of triamterene found was the sulfate conjugate. The area under the curve of this metabolite amounted to 6.672 +/- 2.120 and 11.941 +/- 5.005 micrograms/ml X h after the of 150 mg and 300 mg triamterene doses, respectively. The urinary excretion of the metabolite varied between 25.0 +/- 4.0% and 17.5 +/- 3.5% of the dose after either dose. In healthy subjects an effect on sodium excretion was observed after a dose of 150 mg, whereas the potassium-retaining effect was observed only after the dose of 300 mg.

Administration, Oral↗
PubMed1978

[Errors in clinical data collection (author's transl)].

In the design of clinical trials the collection of the routine data is often not sufficiently defined. Numerous mistakes may occur in the registration of blood pressure, heart rate, body temperature, body weight, circumferences. The mistakes have to be prevented by standardization. In particular the intake of drugs especially during long-term medication has to be supervised.

Body Height↗
PubMed1978

3H-Cymarol in man. Excretion pathways and serum protein binding.

In 10 patients, 5 having received 3H-cymarol i.v., 5 orally, the radioactivity in plasma, urine and in the feces of some patients also was determined. After oral administration the plasma levels rose rapidly reaching maximum levels 1--2 h after administration. After i.v. injection about 30% of the given radioactivity were excreted in the urine. The remaining radioactivity was found in the feces suggesting a high biliary excretion. Only 10% of the radioactivity excreted in the first 24 h were chloroform-extractable. The radioactivity found in the urine after oral administration of the drug amounted to 17.6%. Between 51.1 and 58.5% of the drug were bound to serum proteins.

Aged↗