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Biomedical subjects

H Grobecker

Publications and source records attributed to H Grobecker.

At least 37 records · Page 2Linked to original sources
PubMed1989

Pharmacokinetics of ciprofloxacin in elderly patients.

For perioperative prophylaxis 200 mg ciprofloxacin were administered as a short intravenous infusion to 17 patients aged 57-84 years before transurethral resection (TUR-P) or transvesicular enucleation (TVP) of the prostate. 13 patients were injected simultaneously with 2.5 g ioxitalamic acid i.v. to determine the kidney function. In 11 patients the plasma concentrations were assayed and the pharmacokinetic parameters calculated. At the end of infusion the concentrations of ciprofloxacin in plasma reached 4.2 +/- 0.8 microgram/ml and decreased after a fast distribution period (plasma half-life 0.20 +/- 0.09 h) with a terminal half-life of 4.2 +/- 1.3 h to 0.2 +/- 0.09 microgram/ml after 10 h. The apparent volume of distribution in steady state was 183 +/- 45% of body weight, the plasma clearance 457 +/- 146 ml/min/70 kg. The average concentrations in prostatic adenoma tissue were at all sampling times higher (2fold) than in plasma. The mean concentrations in prostatic secretion were about half of the respective plasma concentrations. High concentrations of the concomitantly administered ioxitalamic acid in prostatic secretion are considered as an indicator of urinary contamination. In those patients high ciprofloxacin concentrations in prostatic secretion are not reliable.

Adenoma↗
PubMed1988

The absolute systemic availability of a new oral formulation of co-dergocrine in healthy subjects.

We have studied the absolute systemic availability (f) of an oral formulation (Hydergin spezial = Hydergine FASR 4 mg per tablet) of co-dergocrine by three different methods. Twelve healthy volunteers received single doses of 0.9 mg co-dergocrine intravenously and 8.0 mg orally in a randomized crossover design. The pharmacological effect of co-dergocrine was monitored as a reduction in plasma prolactin. Maximal plasma concentrations of co-dergocrine after oral dosing ranged between 0.181 and 1.307 ng.ml-1. Maximal urinary excretion ranged between 4.7 and 9.9 micrograms.h-1 and between 0.3 and 2.3 micrograms.h-1 after intravenous and oral doses respectively. Clearance was measured as 90 +/- 22 l.h-1 and the absolute systemic availability (f) as 2.25 +/- 0.65% by using the areas under the plasma concentration-time curves extrapolated to infinity. Calculation of f by comparing areas up to 32 h or the fractions of the dose excreted in urine led to identical results. The intravenous and oral doses produced similar pharmacological effects (reduction of plasma prolactin concentrations) despite the small value of f.

Administration, Oral↗
PubMed1988

Beta-adrenergic receptors and enzymes in rat myocardial membranes: implications of fractionation procedures and beta-adrenoceptor antagonists.

1. We performed an enzymatic characterization of two different fractionation procedures of ventricles from rat hearts. The enzymatic assays covered succinic dehydrogenase as a marker for inner mitochondrial membranes, monoamine oxidase as a marker for outer mitochondrial membranes, NADPH-cytochrome c reductase and RNA as endoplasmatic reticular markers, acid phosphatase as a lysosomal marker, and lactic dehydrogenase as a marker for the "soluble" compartment; DNA was estimated for nuclear contamination. 2. The plasma membrane markers 5'-nucleotidase, Ca2+-ATPase, Mg2+-ATPase, Na+-K+-ATPase, and adenylate cyclase were determined. 3. The roughly prepared membrane fractions showed increased yields of the membrane markers; the number of beta receptors, determined with (-)-[3H] dihydroalprenolol and DL-propranolol, amounted to 68 +/- 6 fmol/mg protein (KD = 3390 +/- 450 pmol, Hill coefficient = 1.5). 4. The membrane fraction prepared with a linear sucrose gradient showed an increased inner mitochondrial membrane marker; presumably the outer mitochondrial membrane was stripped off. The beta-receptor number was 39 +/- 3 fmol/mg protein (KD = 6250 +/- 300 pmol; Hill coefficient = 1.2).

Animals↗
PubMed1988

In-vitro activity of fleroxacin against isolates causing complicated urinary tract infections and concentrations in seminal and prostatic fluid and in prostatic adenoma tissue.

Fleroxacin is a new fluoroquinolone with a broad antibacterial spectrum and a serum half-life of about 8-12 h. Eighty percent of 400 isolates from complicated or hospital-acquired urinary tract infections were inhibited by a concentration of 1 mg/l and 95% by 4 mg/l. As with other quinolones, fleroxacin is less active in acid urine (pH 5.4) than in Mueller-Hinton broth (pH 7.4). In 12 healthy volunteers the concentrations of fleroxacin were measured in plasma and seminal and prostatic fluid 2, 4 and 12 h after an oral dose of 400 mg. The mean plasma concentrations of three or four volunteers at each time were 4.2, 3.6 and 1.2 mg/l, respectively. The corresponding prostatic fluid/plasma ratios were 0.30, 0.27 and 1.96, respectively. By concomittant administration of ioxitalamic acid it could be demonstrated that in samples obtained 12 h after administration urinary contamination must be considered. Fleroxacin is concentrated in seminal fluid by a median ratio of 1.7. In 13 elderly patients the prostatic fluid and prostatic adenoma tissue concentrations were determined one to four hours following oral administration of 400 mg. The concentrations in prostatic fluid were similar to those of volunteers. The tissue concentrations exceeded plasma concentrations by only about 10% (median). Fleroxacin is very active against isolates causing complicated UTI. Concentrations in seminal and prostatic fluid and prostatic adenoma tissue are sufficiently high to treat bacterial prostatitis or vesiculitis caused by susceptible bacterial strains.

Adult↗
PubMed1988

Penetration of fleroxacin into prostatic secretion and prostatic adenoma tissue.

In 12 elderly patients, plasma, prostatic secretion and adenoma tissue concentrations of fleroxacin were determined 1-4 h following oral administration of 400 mg. The plasma concentrations ranged between 0.4 and 5.5 micrograms/ml (median 3.7 micrograms/ml), the mean tissue concentrations were slightly higher. The concentrations in prostatic secretion were about one third of the simultaneous plasma concentrations. High concentrations of the concomitantly administered ioxithalamic acid in prostatic secretion are considered as indicative of urinary contamination, and in this case the fleroxacin concentrations are questionable. The drug levels in prostatic adenoma tissue were similar to the concomitantly measured plasma levels.

Administration, Oral↗
PubMed1987

[The bioavailability of midodrin and alpha-2,5-dimethoxyphenyl-beta-aminoethanol hydrochloride].

The pharmacokinetics of midodrin (alpha-2,5-dimethoxyphenyl-beta-glycinamidoethanol hydrochloride, ST 1085) and its main metabolite ST 1059 (alpha-2,5-dimethoxyphenyl-beta-aminoethanol hydrochloride) have been investigated in 12 male healthy volunteers. 2.5 mg midodrin hydrochloride were applied intravenously, as drinking solution or as tablet (Gutron) according to a randomized cross-over design. Plasma and urine samples collected up to 24 h after application were analyzed by high-performance liquid chromatography with fluorescence detection. The mean maximum concentration in plasma for midodrin was ca. 10 ng/ml 20-30 min after oral administration, for ST 1059 ca. 5 ng/ml after 1 h. Midodrin was eliminated with a terminal half-life of 0.5 h. The half-life of ST 1059 was determined to be 3 h. The mean area under the plasma-level vs. time curve (AUC) of ST 1059 after administration of 2.5 mg midodrin i.v. was 28.7 ng X h/ml, and as drinking solution or as tablet 25.7 and 25.6 ng X h/ml, respectively. The data of 10 volunteers could be used for the calculations of the bioavailability of ST 1059 by the AUC. Assuming an interval of equivalence of 0.75-1.25 because of the relatively small number of volunteers, the three galenical formulations are considered to be equivalent.

Administration, Oral↗
PubMed1987

[Bioavailability of heptaminol in healthy subjects].

In ten healthy volunteers the plasma and urine concentrations of heptaminol (Heptylon) were determined by high-performance liquid chromatography after intravenous administration of 250 mg heptaminol and oral intake of 2 x 150 mg heptaminol in tablet form, and the pharmacokinetic parameters were calculated. Heptaminol was rapidly and entirely absorbed following oral administration of heptaminol. Mean plasma peak concentrations of 1.6 mg/l were reached after 1.8 h, the area under the plasma concentration-time curve was equal to that after intravenous administration. The dominant terminal plasma half-life was 2.5-2.7 h. The total clearance amounted to 700 ml/min, and nearly all the dose given was recovered unchanged in urine within 24 h, indicating renal elimination by glomerular filtration and tubular secretion without metabolization.

Administration, Oral↗
PubMed1986

Pharmacokinetics, in-vitro activity, therapeutic efficacy and clinical safety of aztreonam vs. cefotaxime in the treatment of complicated urinary tract infections.

The minimal inhibitory concentrations (MICs) of aztreonam and cefotaxime were determined against 400 isolates from urological in-patients with complicated and/or hospital acquired urinary tract infections (UTI). Against the Gram-negative rods the activities of both antibiotics were comparable except for higher activity of aztreonam against Pseudomonas aeruginosa. The pharmacokinetic study in nine elderly patients showed a prolonged plasma half life of aztreonam (2.7 h) as compared to younger volunteers (1.6-1.9 h). In a prospective randomized study 39 urological patients with complicated and/or hospital acquired UTI were treated with 1 g aztreonam or cefotaxime iv twice daily for 4 to 15 days. Cure was obtained in 5 out of 18 patients in the aztreonam and 7 out of 20 patients in the cefotaxime group. There were 3 superinfections, 7 relapses and 3 reinfections in the aztreonam group and 1 failure, 1 superinfection, 6 relapses and 5 reinfections in the cefotaxime group. There was no significant difference in therapeutic efficacy between the two antibiotics. Both antibiotics were tolerated well and seem to be equally effective in the treatment of complicated UTI caused by sensitive organisms.

Adult↗
PubMed1986

Inhibition of monoamine oxidase by viloxazine in rats.

Biochemical and pharmacological investigations about the effect of the antidepressant drug viloxazine (Vivalan) on catecholamine metabolism in rats led to the following results: Viloxazine exerts a dose and time dependent inhibition of monoamine oxidase activity of brain and liver mitochondrial fraction and tissue homogenates of hypothalamus, heart, liver, and adrenal glands, both in vitro and after oral and parenteral administration in vivo. Consequently, an increase in catecholamine concentrations in brain of rats could be observed after pretreatment with viloxazine. In addition brain serotonin concentrations rose and 5-hydroxy-indoleacetic acid was diminished. However, characterization of inhibition of monoamine oxidase activity by viloxazine in vitro revealed: Compared to the specific inhibitors clorgyline for MAO-A- and pargyline for MAO-B-activity, viloxazine was a very weak inhibitor both for MAO-A and MAO-B in vitro. The type of inhibition was competitive and reversible. From the presented results and the results obtained by other laboratories it is concluded that inhibition of monoamine oxidase activity by viloxazine, although clearly demonstrated in animal experiments, may not be the only mechanism for an antidepressant action of the drug in man.

Animals↗
PubMed1986

[The sympatho-adrenal system. Implications for the pathogenesis, diagnosis and therapy of cardiac arrhythmias].

Changes in biosynthesis, storage, release and inactivation of the catecholamines noradrenaline and adrenaline, as well as in the dynamic regulation and localization (internalization/externalization) of post- and presynaptic alpha- and beta-receptors and their subpopulations have implications for the pathogenesis of cardiac arrhythmias. Circulating levels of plasma catecholamines provide a reliable biochemical index for sympatho-adrenal activity and reactivity as well as for diagnosis and prognosis of these arrhythmias. Therapeutic interventions should consequently prefer blockade of myocardial alpha- and/or beta-adrenoceptors, especially after postischaemic arrhythmias with externalization of beta-adrenoceptors.

Arrhythmias, Cardiac↗
PubMed1985

Effects of nicotine and its major metabolites on blood pressure in anaesthetized rats.

Blood pressure and heart rate in anaesthetized rats has been determined after i.v. injection of increasing doses of nicotine (NI) and its major metabolites, i.e. continine (CO), nornicotine (NOR), metanicotine (MN) and dihydrometanicotine (DMN). NI and MN elicited similar dose response curves, increasing blood pressure according to the dose injected. However, the dose response curve of MN was shifted to the right. Furthermore DMN caused similar pressor effects than MN and the pressor effects of NOR was even weaker. Only after injection of CO was a dose-dependent depressor effect observed and this was reversed after very high doses. CO also reduced heart rate in a dose-dependent manner, whereas NI and its other metabolites did not significantly change heart rate.

Animals↗
PubMed1985

Sympathoadrenal dysfunction in rats with chronic neurogenic hypertension.

Compared to sham-operated controls 5 weeks after surgery neurogenic hypertensive rats with sino-aortic baroreceptor deafferentation had higher blood pressure, higher plasma noradrenaline and adrenaline levels, lower heart noradrenaline concentrations, higher adrenomedullary adrenaline levels and increased cardiac intraventricular pressure (dp/dtmax).

Adrenal Glands↗
PubMed1985

Changes in plasma catecholamine concentrations in patients with coronary heart disease during pacing and physical exercise.

To study the difference in sympathetic activity during pacing the right atrium or during physical exercise in patients with coronary heart disease, we investigated circulating plasma catecholamine concentrations in the coronary sinus and brachial artery radioenzymatically in 11 male patients with well documented coronary artery disease. Heart rate was increased stepwise 20 beats/min from 90 beats/min up to 150 beats/min by pacing the right atrium and physical exercise was performed by increasing work load stepwise by 25 from 25 up to 100 W on an ergometric bicycle. Plasma noradrenaline and adrenaline concentrations were increased significantly only during physical exercise. In addition, there was an increase in arterial-coronary sinus noradrenaline difference during graded physical exercise, whereas no further release of noradrenaline from the myocardium occurred during pacing. An enhanced cardiac sympathetic tone in patients with coronary heart disease is discussed. It is suggested that atrial pacing is not an adequate stimulus evoking an overall increase of cardiac and peripheral sympathetic tone.

Cardiac Pacing, Artificial↗
PubMed1985

Effect of ketanserin on hemodynamics, plasma-catecholamine concentrations, and serotonin uptake by platelets in volunteers and patients with congestive heart failure.

Ketanserin, which preferentially blocks 5-HT2-serotonergic receptors, was injected intravenously (i.v.) to patients with congestive heart failure in a bolus dose of 10 mg, followed by an i.v. infusion of 3 mg/h over a period of 4 h. The drug caused a decrease in total peripheral resistance and, conversely, an increase in stroke volume. Right atrial and pulmonary artery pressures were decreased. Plasma noradrenaline rose twofold over the basal levels shortly after injection, but showed a distinct fall 2 h after beginning of the treatment. The concentrations of ketanserin in plasma after bolus injection approximated 100-150 ng/ml. The sympathoneuronal and sympathoadrenal reaction during tilting were increased after i.v. injection of 10 mg ketanserin in volunteers. The noradrenaline and adrenaline levels in plasma rose significantly more when compared with values before the injection of the drug. In vitro as well as in vivo ketanserin exerts a concentration-dependent inhibitory effect on the active transport of serotonin and catecholamines (dopamine, noradrenaline, adrenaline) into human platelets. Considering platelets as a model of the sympathetic neurons, the inhibition of reuptake of catecholamines by ketanserin could contribute to the observed increase in circulating catecholamines after injection of the drug.

Aged↗
PubMed1985

High-performance liquid chromatography analysis of mezlocillin, piperacillin, their degradation products, and of ioxitalamic acid in plasma and urine of healthy volunteers.

In plasma and urine of 10 healthy volunteers after intravenous administration of 4 g mezlocillin and piperacillin, respectively, the parent compounds as well as degradation products were assayed by high-performance liquid chromatography. Ioxitalamic acid, a renal contrast medium, was administered simultaneously, in order to measure the glomerular filtration rate, and to control the collection of 24-h urine. As metabolite of mezlocillin the corresponding penicilloic acid only was found, whereas in the case of piperacillin a further degradation product was observed. Half of the doses given was recovered in the urine as unchanged drugs, and in addition 5-10% as metabolites. No differences were found in the pharmacokinetic behaviour of both antibiotics.

Adult↗
PubMed1984

High-performance liquid chromatographic analysis of cefotetan epimers in human plasma and urine.

Cefotetan, a new broad-spectrum 7 alpha-methoxycephalosporin antibiotic, was assayed in plasma and urine by means of reversed-phase high-performance liquid chromatography. Commercially available cefotetan exists in two epimeric forms. The procedure described allows the separation and quantitation of both epimers. For the first time a different pharmacokinetic behaviour (t1/2 = 3 h versus 4 h) for each epimer after intravenous injection to healthy volunteers is demonstrated. It is assumed that one epimer is bound to a greater extent to serum proteins and is therefore responsible for the differences observed. As both epimers exhibit similar antibacterial activity, it seems doubtful whether these differences would have clinical significance. Iothalamic acid was determined simultaneously as a marker of kidney function.

Biological Assay↗
PubMed1984

Changes in peripheral and central catecholaminergic and serotoninergic neurons of rats after acute and subacute administration of nicotine.

To establish dose-response relationships for nicotine (acute and subacute administration), we measured hemodynamic parameters as well as circulating and tissue catecholamines in sympathetically innervated organs in rats. We also investigated nicotines's influence on adrenoceptor binding sites of the heart and on serotonin metabolism. In conscious and anesthetized rats, we found a dose-dependent increase in circulating catecholamines after acute injection of nicotine. At low doses nicotine released norepinephrine, resulting in a decrease of blood flow and heart rate, whereas high doses of nicotine released epinephrine, resulting in a reversal of the cardiovascular parameters investigated. In the heart norepinephrine concentration increased after nicotine application. In the lung epinephrine rose markedly, whereas serotonin and 5-hydroxyindolacetic acid were diminished. After subacute administration of nicotine the number of binding sites for 3H-Dihydroalprenolol in the heart was significantly reduced, whereas norepinephrine content was increased. Dopamine, serotonin, and 5-hydroxyindolacetic acid were increased in the hypothalamus. Our findings show that nicotine not only affects peripheral and central catecholaminergic neurons, but also central serotoninergic neurons, thus enhancing turnover of these amines.

Adrenal Medulla↗