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Biomedical subjects

H Grobecker

Publications and source records attributed to H Grobecker.

At least 19 recordsLinked to original sources
PubMed2001

Determination of opipramol in human plasma by high-performance liquid chromatography with photometric detection using a cyanopropyl column.

A high-performance liquid chromatographic method is described for the determination of opipramol in human plasma. Opipramol was extracted into tert.-butylmethyl ether, separated on a cyanopropyl silica column and detected at 254 nm. Imipramine was used as internal standard. The limit of quantitation was 250 pg/ml using 1.5 ml plasma. Precision was better than 9%, inaccuracy less than 8%. The assay is more sensitive than previously published methods, and it has been applied to the analysis of plasma samples from a pharmacokinetic study.

Antidepressive Agents, Tricyclic↗
PubMed2001

Pharmacokinetics of therapeutic doses of tropisetron in healthy volunteers.

AIMS: To establish the bioavailability of tropisetron (5 mg) administered orally as capsule compared with 2 mg given intravenously. METHODS: Using a randomized crossover design, 18 healthy volunteers received a single oral dose of tropisetron (5 mg) and an intravenous bolus of tropisetron (2 mg) separated by a wash-out period of 1 week. Plasma concentrations of tropisetron were determined by h.p.l.c. and the pharmacokinetic parameters were estimated. RESULTS: The mean pharmacokinetic parameters for 5 mg tropisetron given orally were Cmax 3.46 ng ml(-1), t(max) 2.6 h, t(1/2) 5.7 h and AUC(0,infinity) 32.9 ng ml(-1) h. After intravenous administration initial plasma concentration was 15.1 ng ml(-1), t(1/2) 5.6 h, AUC(0,infinity) 20.7 ng ml(-1) h, V 678 l and CL 1800 ml min(-1). An inverse correlation was demonstrated between CYP2D6 activity, measured by the sparteine metabolic ratio, and the bioavailability (mean 0.60, range 0.27-0.99) of oral tropisetron. CONCLUSIONS: Tropisetron exhibits a wide range of oral bioavailability at therapeutic doses, which is mainly determined by CYP2D6 activity.

Administration, Oral↗
PubMed2000

Pharmacokinetic interaction between proton pump inhibitors and roxithromycin in volunteers.

BACKGROUND: Triple therapy including two antibiotics and a proton pump inhibitor is a rational approach to the treatment of Helicobacter pylori induced peptic ulcer disease. The interaction of antimicrobial therapy and acid suppression is not yet well elucidated. AIMS: To investigate the effects of proton pump inhibitors on roxithromycin levels in plasma and gastric tissue under steady-state conditions in volunteers. METHODS: In two crossover studies omeprazole 20 mg b.d., lansoprazole 30 mg b.d., roxithromycin 300 mg b.d., and the combination of roxithromycin with either omeprazole or lansoprazole were administered to 12 healthy volunteers over 6 days. Blood plasma levels of the drugs were measured. In addition, roxithromycin concentrations were also determined in gastric juice and gastric tissue obtained during endoscopy. RESULTS: The proton pump inhibitors and roxithromycin did not alter the blood plasma pharmacokinetics of each other. When compared to roxithromycin administered alone, its combination with a proton pump inhibitor significantly increased the roxithromycin concentrations in gastric juice (3.0-5.0 microg/mL vs. 0.3-0.4 microg/mL) and gastric tissue (antrum: 3.8-4.0 vs. 2.8 microg/g, fundus: 5.9-7.4 vs. 4.2-4.4 microg/g). CONCLUSIONS: Proton pump inhibitors and roxithromycin do not alter the systemic bioavailability of each other. However, proton pump inhibitors increase the local concentration of roxithromycin in the stomach which may contribute to the clinically proven synergic beneficial action in eradication therapy of H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2000

Effect of tropisetron on circulating catecholamines and other putative biochemical markers in serum of patients with fibromyalgia.

OBJECTIVE: The aim of the study was to assess the influence of the 5HT3-receptor antagonist tropisetron on circulating catecholamines as biochemical markers of the activity of the sympathoadrenal system in fibromyalgia. Moreover, serum concentrations of serotonin, somatomedin C, oxytocin, calcitonin-gene-related-peptide, calcitonin and cholecystokinin were assayed as putative markers in pain-related disorders like primary fibromyalgia. METHODS: In 96 patients, who met the ACR classification criteria for fibromyalgia, and in 20 sex and age matched controls concentrations of dopamine, noradrenaline, adrenaline, serotonin and tropisetron were assayed in serum by HPLC with electrochemical detection. All other transmitters were determined by ELISA. RESULTS: There was with the exception of tropisetron, calcitonin and dopamine, no correlation between doses of tropisetron 5, 10, 15 mg respectively and significant changes in circulating transmitters or other transmitters as putative biochemicals markers in primary fibromyalgia. Regarding the prediction of pain reduction to tropisetron, patients with elevated dopamine and/or reduced plasma 5-HT concentrations tended to show a higher response rate. CONCLUSION: Despite these partly disappointing results another prospective pilot study with selected patients vs. age and sex matched controls, double blind and with comparison of other 5HT3-receptor antagonists e.g. dolasetron and granisetron e.g. after i.v. bolus injection is suggested. Still the data obtained in this preliminary paper provide some evidence regarding the present discussion on subgroups of patients with primary fibromyalgia.

Analysis of Variance↗
PubMed1996

Simultaneous determination of acetylsalicylic acid and salicylic acid in human plasma by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method is described for the simultaneous determination of acetylsalicylic acid (ASA) and its main metabolite salicylic acid (SA) in human plasma. Acidified plasma is deproteinized with acetonitrile which is separated from the aqueous layer by adding sodium chloride. ASA and SA are extracted into the acetonitrile layer with high yield, and determined by reversed-phase HPLC (column: Novapak C18 4 microns silica, 150 x 4 mm I.D.; eluent: 740 ml water, 900 microliters 85% orthophosphoric acid, 180 ml acetonitrile) and photometric detection (237 nm). 2-Methylbenzoic acid is used as internal standard. The method allows the determination of ASA and SA in human plasma as low as 100 ng/ml with good precision (better than 10%). The assay was used to determine the pharmacokinetic parameters of ASA and SA following oral administration of 100-500 mg ASA in healthy volunteers.

Analgesics, Non-Narcotic↗
PubMed1996

Bioavailability of cefpodoxime proxetil with co-administered acetylcysteine.

In a cross-over study on twelve healthy volunteers cefpodoxime proxetil (CAS 87239-81-4) and acetylcysteine (CAS 616-91-1) were evaluated for possible pharmacokinetic interactions. After a standardized breakfast, the subjects received p.o. either 200 mg cefpodoxime administered as cefpodoxime proxetil (reference) or 200 mg cefpodoxime and 200 mg acetylcysteine (test). To determine the pharmacokinetic profile of cefpodoxime the plasma concentrations were determined by HPLC. The plasma concentration-time curve of cefpodoxime was very similar after both regimens, and with respect to cefpodoxime bioequivalence has been proven. The narrow range of 90% confidence intervals for the quotient test/reference for Cmax and AUC indicate reliable bioavailability of cefpodoxime proxetil independent of co-administered acetylcysteine.

Acetylcysteine↗
PubMed1992

Cardiovascular parameters and catecholamines in volunteers during passive orthostasis. Influence of antihypotensive drugs.

To evaluate the therapeutic value of various antihypotensive agents we investigated amezinium (AMZ; CAS 30578-37-1), dihydroergotamine (DHE; CAS 511-12-6), midodrine (MDD; CAS 42794-76-3), and oxilofrine (OXF; CAS 365-26-4) in volunteers during passive orthostasis in a randomized double-blind study against placebo (PCB). Blood pressure, heart rate, and circulating catecholamines were determined before and after i.v. injections of the mentioned agents before and during 10 min of passive orthostasis. Echocardiographic and venous plethysmographic data were obtained during resting before and after the administration of the drugs. Resting heart rate decreased after injection of PCB, AMZ, DHE, and MDD. During tilting no significant changes in heart rate could be observed. Blood pressure remained unchanged at rest and during orthostasis after all agents injected. DHE and MDD lowered circulating noradrenaline. Echocardiographic parameters were changed after administration of AMZ (increase in stroke volume index (SVI) and ejection fraction (EF)), MDD (increase in enddiastolic volume index and SVI), and OXF (increase in SVI, EF, and cardiac index). The venous capacity of the lower left leg was only significantly decreased after injection of DHE, indicating an increased venous tone of the leg veins. The observed changes in sympathetic and cardiovascular parameters are in agreement with their sympathomimetic actions and allow a differential therapeutic classification: DHE and MDD are suitable agents for patients with sympathotonic orthostatic reaction; if asympathotonic orthostatic reaction occurs MDD, AMX and OXF should be recommended to those patients.

Adult↗
PubMed1992

[Structural characterization of an unknown metabolite of ciprofloxacin].

The chemical structure of an unknown metabolite of ciprofloxacin (CAS 85721-33-1) is characterized by means of reversed phase ion pair liquid chromatography, absorption and fluorescence spectroscopy, partition coefficients as well as chemical and enzymatic hydrolytic degradation. A chemical structure of the unknown metabolite is proposed: N-formyl-desethylen-ciprofloxacin. It can be formed as an intermediate in the oxidative degradation of ciprofloxacin via oxociprofloxacin to desethylen-ciprofloxacin, or it may be formed by conjugation of desethylen-ciprofloxacin with formic acid. The amounts found in plasma and urine of patients were in the range of desethylen-ciprofloxacin, i.e. about 1% of the parent compound.

Biotransformation↗
PubMed1991

Comparative investigations on the bioavailability of cefuroxime axetil.

In a three-way cross-over study the bioavailability of cefuroxime was determined in 12 healthy volunteers after oral administration of 250 mg as cefuroxime axetil (Elobact; CAS 64544-07-6) in a plain aqueous suspension and as tablets from different batches. The tablet formulations showed nearly identical pharmacokinetic parameters and were bioequivalent. The mean maximum serum concentration was 4.7 micrograms/ml, achieved after 2.1 h. The serum half-live was 1.2-1.4 h, the area under the serum concentration-time curve was 14.3-14.4 micrograms/ml.h and the urinary recovery of unchanged cefuroxime was 54%. The bioavailability of cefuroxime after administration of cefuroxime axetil in aqueous suspension was lower, but bio-inequivalence was not demonstrated.

Adult↗
PubMed1990

Pharmacology and clinical pharmacology of organic nitrates.

Current concepts and future aspects of pharmacological interventions in the treatment of coronary heart disease have been compiled. Especially new insights in the pathophysiology of coronary heart disease e.g. the dynamic pathology of coronary atherosclerosis, possible role of endothelin in vasospasm, as well as new pharmacodynamic and pharmacokinetic aspects of organic nitrates are discussed. Also the role of sympathetic nervous system as a pivotal question in pathophysiology and clinical pharmacology in the treatment of angina pectoris has been considered.

Adrenergic beta-Antagonists↗
PubMed1990

Skin tissue fluid levels of cefotiam in healthy man following oral cefotiam hexetil.

Cefotiam hexetil is a pro-drug of cefotiam available for oral administration. To evaluate cefotiam concentrations at the active site in skin and soft-tissue infections, drug levels in skin suction blister fluid (SBF), cantharides blister fluid (CBF) and serum were determined. Six healthy subjects received oral cefotiam 400 mg as cefotiam hexetil. On an other day 200 mg was injected intravenously. Following the oral dose, the bioavailability of cefotiam was 45.5%, and the maximum concentration in serum of 2.6 mg.l-1 was obtained at 2.1 h. Peak concentrations in both types of blister fluid (0.9 mg.l-1) were significantly lower than after the iv dose (SBF 1.4 mg.l-1, CBF 1.5 mg.l-1), and the peak levels occurred later (3.3 versus 1.5 h in CBF). Despite the delay, the extent of penetration was about 100% following either mode of administration (SBF, iv dose 112%, oral dose 117%). The cefotiam level in skin blister fluids declined significantly more slowly than the serum level. Following the oral dose, the mean terminal half life was serum 0.8 h, SBF 2.6 h and CBF 4.6 h. Cefotiam concentrations in the blister fluids were close to the MIC90 of Staphylococcus aureus, S. epidermis and H. influenzae and exceeded the MIC90 of Streptococci, E. coli and Proteus mirabilis. Thus, the oral administration of cefotiam 400 mg t.i.d. should be curative in the majority of bacterial infections of the skin and soft-tissues.

Administration, Oral↗
PubMed1990

Adrenaline in cardiovascular diseases--effect of beta-adrenoceptor antagonists.

By subcutaneous insertion of osmotic minipumps leading to continuous infusion of l-adrenaline, we were able to induce hypertension in normotensive Wistar-Kyoto strain (WKY) rats which was shown to be completely reversible by application of the non-selective beta-adrenoceptor antagonist carvedilol. No consistent effect of adrenaline on heart rate could be observed. At least in rat heart, adrenaline replaced the original neurotransmitter noradrenaline in amine storage sites, the sum of all catecholamines remaining unchanged. By comparing tissue concentrations of endogenous amines of spontaneously hypertensive rats (SHR) and stroke-prone-SHR (SHR-SP) to the corresponding levels of their normotensive controls of the Wistar-Kyoto strain, we detected various differences in amine handling during the development of high blood pressure. Significant increases of adrenal gland catecholamines at the ages of 8 and 14 weeks are accompanied by striking alterations of catecholamine (CA) storage in other peripheral organs like the heart and kidneys. Most prominent increases, as compared to controls, were found in adrenaline concentrations in heart and kidney at all ages studied, with levels two to four times higher than the respective WKY concentrations. The results are compatible with a permissive role of adrenaline as a cotransmitter in the initiation and/or maintenance of hypertension. After incorporation into endogenous amine storage vesicles, e.g., of the heart, adrenaline is probably released, together with noradrenaline, upon nerve stimulation. By stimulating presynaptic beta 2-adrenoceptors, adrenaline is able to facilitate noradrenaline release and to enhance noradrenergic vasoconstriction. The resulting increase of peripheral sympathetic tone may be responsible for the pathogenesis of rat genetic and human essential hypertension, as well as for the triggering of myocardial infarction. The blockade of presynaptic beta-receptors is supposed to represent an important mechanism of action of non-selective beta-blocking agents. In the case of carvedilol, this effect is supported by additional antagonism at vascular alpha-adrenoceptors, leading to vasodilation.

Adrenergic beta-Antagonists↗
PubMed1990

[The bioavailability of doxycycline].

The bioavailability of doxycycline (Doxy-Diolan 100 tablets, test, active substances: 100 mg doxycyclin per tablet) was compared with that of another commercially available tablet-formulation containing the same active substance (reference). In a cross-over study, 16 young healthy male volunteers were administered in fasting state orally by one tablet containing 100 mg active substance. The concentrations of doxycycline were determined in plasma and saliva by a high-performance liquid chromatographic assay. Mean maximum plasma concentration (cmax +/- standard deviation) of doxycycline were 1.57 +/- 0.40 micrograms/ml (test) and 1.59 +/- 0.38 micrograms/ml (reference), respectively, and were reached 1.47 +/- 0.55 h and 1.66 +/- 0.57 h after administration. Plasma half-lives were 16.6 +/- 2.9 h and 16.8 +/- 3.0 h, the areas under the plasma concentration-time curves (AUC0-00) 29.3 +/- 4.5 mg/l.h and 29.7 +/- 4.4 mg/l.h. The concentration of doxycycline in saliva were low, median maximum concentrations of 50 ng/ml were measured 1-2 h after administration. The statistical evaluation revealed bioequivalence between both drugs.

Adult↗
PubMed1990

Relative bioavailability of three cefixime formulations.

Three galenic formulations of cefixime (tablet, syrup and dry suspension) containing 200 mg each were compared with respect to their relative bioavailability in twelve healthy volunteers. All three formulations showed reliable absorption. Mean peak plasma concentrations were reached after 3.3-3.5 h, mean terminal half lives were 2.9-3.1 h. 18-24% of the dose administered were recovered unchanged in the urine. Best bioavailability was obtained with the dry suspension (AUC0-infinity = 25.8 +/- 7.0 micrograms/ml h; Cmax = 3.4 +/- 0.9 microgram/ml), followed by the tablet (AUC0-infinity = 20.9 +/- 8.1 micrograms/ml h; Cmax = 3.0 +/- 1.0 micrograms/ml) and the syrup which is based on triglycerides (AUC0-infinity = 17.8 +/- 5.9 micrograms/ml h; Cmax = 2.4 +/- 0.7 micrograms/ml). The statistical analysis resulted in bioinequivalence between dry suspension and syrup. It is concluded that best bioavailability of cefixime after oral administration is guaranteed when taken in an "aqueous medium" either as dry suspension or as tablet with "plenty of liquid".

Administration, Oral↗
PubMed1989

Distribution and subtype determination of beta-receptors in the spinal cord of the adult rat.

1. We determined the number of beta-receptors in the whole spinal cord of the adult rat and in the cervical, thoracal, and lumbal/sacral parts. 2. The undivided spinal cord contains 47 +/- 10 fmol/mg beta-receptors (KD = 2066 +/- 982 pmol/liter), and the cervical part of the spinal cord contains 53 +/- 8 fmol/mg protein (KD = 3224 +/- 1775 pmol/liter). The thoracal part shows 40 +/- 1 fmol/mg protein (KD = 3229 +/- 104 pmol/liter), and the lumbal/sacral spinal cord contains 48 +/- 8 fmol/mg protein (KD = 3610 +/- 1610 pmol/liter). 3. Competitive inhibition studies with l-practolol, dl-atenolol, and ICI 118,551 were performed and we calculated by a computer program in the whole spinal cord the following ratio of beta-receptor subtypes: 80 +/- 5% Beta 1-receptors and 20 +/- 5% beta 2-receptors. 4. The basal and (-)-isoproterenol- and NaF-stimulated activity of adenylate cyclase was highest in the cervical part of the spinal cord and equally distributed between the thoracal and the lumbal/sacral parts. 5. The whole synaptosomal protein of the cervical part of the spinal cord contained 132 +/- 20 fmol, the thoracal part 117 +/- 3 fmol, and the lumbal/sacral part 133 +/- 22 fmol.

Adenylyl Cyclases↗