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G Hempel

Publications and source records attributed to G Hempel.

At least 37 records · Page 2Linked to original sources
PubMed1998

Population pharmacokinetic-pharmacodynamic modeling of moxonidine using 24-hour ambulatory blood pressure measurements.

OBJECTIVES: To develop a model for 24-hour ambulatory blood pressure measurements (ABPM) that can be applied in a pharmacokinetic-pharmacodynamic model. METHODS: Four different data sets were prepared from 2 studies to accommodate different modeling strategies. In study A, a double-blind placebo-controlled study in 47 patients, 24-hour ABPM profiles (74 to 99 measurements per profile) were obtained during the placebo run-in phase and after 3, 5, and 11 weeks during the treatment. Three to 5 plasma samples were taken. Cosine and polynomial models were evaluated to describe the circadian rhythm in blood pressure based on 3 data sets (1: only run-in data; 2: only placebo data; 3: all data). In study B, a double-blind placebo-controlled study in 94 patients, two 24-hour ABPM profiles per patient (during placebo run-in and after 8 weeks) were recorded and randomly reduced to 15 measurements per profile to evaluate the robustness of the baseline model. RESULTS: The mean moxonidine clearance was 35 L/h, and the volume of distribution was 132 L. The final baseline model consisted of 2 cosine terms with fixed-effect parameters for rhythm-adjusted 24-hour mean blood pressure, amplitude, phase, and period; random-effect parameters for interindividual variability in rhythm-adjusted 24-hour mean, amplitude, and clock time; and interoccasion variability in rhythm-adjusted 24-hour mean and clock time. The final baseline model was combined with an Emax model for the drug effect. An effect compartment was used (kco = 0.198 h-1). The maximum decrease in diastolic blood pressure (Emax) was 16.7%, and EC50 was 0.945 microgram/L. CONCLUSION: The pharmacokinetic-pharmacodynamic model for 24-hour ABPM can be used to estimate the concentration-effect relationship of antihypertensive drugs.

Aged↗
PubMed1998

Experimental artefacts in 2D-MAS exchange experiments: non-uniform mixing time within a single 2D run.

The practical realization of rotor-synchronized mixing-times in 2D-MAS exchange experiments without the need for a special hardware is reviewed; its consequence for the 'true mixing time' of the experiment is discussed. We demonstrate influences on experimental rate constants derived from such experiments as well as on the appearance of the 2D-MAS spectra, taken at short mixing times.

Artifacts↗
PubMed1998

MAS NMR studies of carbon-13 spin exchange in durene.

One- (1-D) and two-dimensional (2-D) carbon-13 NMR exchange measurements in powder samples of isotopically normal durene under magic angle spinning (MAS) are reported. The experiments include rotor synchronized 2-D exchange (RS2DE), 1-D magnetization transfer (MT) and time reverse ODESSA (tr-ODESSA). The latter two experiments were performed as a function of several external parameters, including proton decoupling field during mixing time, sample spinning rate and partly, of temperature. The effects of these parameters on the spin exchange induced by spin diffusion and by chemical, or physical exchange, is discussed. Spin exchange between all types of carbons in the durene molecules occurs on the time scale of seconds. From the dependence of the spin exchange rate on the external parameters it is concluded that the process is dominated by spin diffusion. On the basis of these results an upper limit of 10(-16) cm2 s(-1) can be set for the self-diffusion constant in crystalline durene.

Benzene Derivatives↗
PubMed1998

Chemically induced isomerization and differential uptake modulate retinoic acid disposition in HL-60 cells.

The successful introduction of 13-cis-retinoic acid (13-cis-RA) and all-trans-retinoic acid (all-trans-RA) in the chemoprevention and treatment of cancer along with the discovery of different retinoic acid receptors transactivated by different retinoic acid isomers resulted in a number of in vitro studies of the antitumor effects of single retinoic acid isomers. Since the formation of retinoic acid isomers with different receptor affinities might modulate retinoic acid response in vitro, we determined retinoic acid disposition in HL-60 cells and cell culture medium during incubation with 13-cis-, 9-cis-, and all-trans-RA. In medium, retinoic acids underwent a thiol-radical mediated isomerization resulting in a mixture of 13-cis-, 9-cis-, 9,13-di-cis-, and all-trans-RA. Except for the 9, 13-di-cis-RA, all isomers generated in medium were also detected in HL-60 cells. Whereas 9-cis-RA and 13-cis-RA showed similar cellular pharmacokinetics, all-trans-RA reached about fourfold higher concentrations in HL-60 cells compared to 9-cis-RA and 13-cis-RA. Due to its better uptake, all-trans-RA became the main isomer within cells as it was formed in the medium when incubated with 13-cis-RA and 9-cis-RA. Thus, due to the simple chemically induced isomerization and its profound influence on cellular retinoic acid concentrations, studies of the efficacy of single retinoic acid isomers in vitro should be interpreted with caution.

Biological Transport↗
PubMed1997

Determination of idarubicin and idarubicinol in plasma by capillary electrophoresis.

A rapid and sensitive capillary electrophoretic method for the determination of idarubicin and its metabolite idarubicinol in plasma has been developed and validated. Plasma is extracted by liquid-liquid extraction using chloroform. Idarubicin, idarubicinol and the internal standard daunorubicin can be separated in less than 5 min using a phosphate buffer of pH 5 with 70% acetonitrile. Laser-induced fluorescence detection with an Ar ion laser operated at 488 nm provides a sensitive and selective detection method without interferences from biological fluids. The small sample volume of 100 microl is of particular advantage for studies in pediatric oncology. The reproducibility of the method has been shown to be sufficient for drug monitoring or pharmacokinetic studies. The limit of quantification for idarubicin in plasma is 0.5 ng/ml.

Antibiotics, Antineoplastic↗
PubMed1997

Pharmacokinetics of trofosfamide and its dechloroethylated metabolites.

To contribute to effective and safe outpatient treatment, we investigated the metabolism of trofosfamide (Trofo) after oral administration. We analyzed Trofo metabolism in 15 patients aged from 3 to 73 years who were treated with 150 or 250 mg/m2 Trofo in combination with etoposide. Serum samples were collected with 13 patients after oral administration, and Trofo and its dechloroethylated metabolites were quantified by gas chromatography. Urine samples were collected from five patients and analyzed by same method. Ifosfamide (Ifo) was the main metabolite in serum and urine (AUCTrofo:AUCIfo 1:13), whereas cyclophosphamide (Cyclo) was formed in smaller amounts (AUC(Ifo):AUC(Cyclo) 18:1). Ifo and Cyclo were further oxidized in the chloroethyl side chains to form 2- and 3-dechlorethylifosfamide in varying quantities. The urinary excretion of Trofo and its dechloroethylated metabolites amounted to about 10% of the total dose. Our results confirm former in vitro observations about the metabolism of Trofo. The main side-chain metabolites Ifo and Cyclo can be further activated by oxidation and formation of their respective phosphoramide mustards. Hence, Trofo is an interesting agent for oral chemotherapy.

Adolescent↗
PubMed1997

Trofosfamide: a review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the oral treatment of cancer.

During the last decade, the oxazaphosphorine trofosfamide was underestimated partly due to its unsuitability for i.v. use. Oral daily doses of 150 mg were tolerated well and showed appreciable response rates in the treatment of lymphoma. Furthermore, activity in sarcoma and cancers sensitive to oxazaphosphorines in general seems probable, because ifosfamide is the main metabolite of trofosfamide. Due to its oral mode of application and good tolerance, trofosfamide will be an important option in view of the increasing demand for treatment regimens suited for an outpatient basis. Results of the major in vitro, in vivo and clinical studies are reported for evaluation of its significance in chemotherapy today.

Administration, Oral↗
PubMed1996

Simultaneous determination of all-trans-, 13-cis- and 9-cis-retinoic acid, their 4-oxo metabolites and all-trans-retinol in human plasma by high-performance liquid chromatography.

All-trans-retinoic acid (all-trans-RA) and 13-cis-retinoic acid (13-cis-RA), due to their effects on cell differentiation, proliferation and angiogenesis, improved treatment results in some malignancies. Pharmacokinetic studies of all-trans-RA and 13-cis-RA along with monitoring of retinoic acid metabolites may help to optimize retinoic acid therapy and to develop new effective strategies for the use of retinoic acids in cancer treatment. Therefore, we developed a HPLC method for the simultaneous determination in human plasma of the physiologically important retinoic acid isomers, all-trans-, 13-cis- and 9-cis-retinoic acid, their 4-oxo metabolites, 13-cis-4-oxoretinoic acid (13-cis-4-oxo-RA) and all-trans-4-oxoretinoic acid (all-trans-4-oxo-RA), and Vitamin A (all-trans-retinol). Analysis was performed on a silica gel column with UV detection at 350 nm using a binary multistep gradient composed of n-hexane, 2-propanol and glacial acetic acid. For liquid-liquid extraction a mixture of n-hexane, dichloromethane and 2-propanol was used. The limits of detection were 0.5 ng/ml for retinoic acids and 10 ng/ml for all-trans-retinol. The method showed good reproducibility for all components (within-day C.V.: 3.02-11.70%; day-to-day C.V.: 0.01-11.34%). Furthermore, 9-cis-4-oxoretinoic acid (9-cis-4-oxo-RA) is separated from all-trans-4-oxo-RA and 13-cis-4-oxo-RA. In case of clinical use of 9-cis-retinoic acid (9-cis-RA) the pharmacokinetics and metabolism of this retinoic acid isomer can also be examined.

Chromatography, High Pressure Liquid↗
PubMed1996

Determination of paclitaxel in biological fluids by micellar electrokinetic chromatography.

A method has been developed for the determination of paclitaxel (Taxol) in plasma and urine using capillary electrophoresis with sodium dodecyl sulfate as additive in the run buffer. The samples are extracted and preconcentrated with tert.-butyl methyl ether. Taxotere has been used as the internal standard. The limit of detection of paclitaxel is 20 ng/ml. In comparison to high-performance liquid chromatography, the capillary electrophoresis method is simple and needs less organic solvents.

Acetonitriles↗
PubMed1996

Direct determination of zolpidem and its main metabolites in urine using capillary electrophoresis with laser-induced fluorescence detection.

Zolpidem is a new sleep inducer belonging to the imidazopyridine class. We wish to report a method for the determination of zolpidem and its main metabolites in urine without extraction using capillary electrophoresis with UV laser-induced fluorescence detection with a He-Cd laser. A 10-nl sample of urine can be directly applied to the capillary. The separation is carried out within 10 min, and the limit of detection is 2 ng/ml. This procedure is very simple and fast. No organic solvents are necessary.

Electrophoresis, Capillary↗
PubMed1996

Enantioselective determination of zopiclone and its metabolites in urine by capillary electrophoresis.

A method has been developed for the stereoselective determination of zopiclone and its main metabolites in urine. After the addition of the internal standard zolpidem the urine samples were extracted at pH 8 with chloroform-isopropanol (9:1). Analyses were carried out using capillary electrophoresis (CE) with beta-cyclodextrin as the chiral selector. The analytes were detected using UV laser-induced fluorescence detection with a He-Cd laser operated at 325 nm. Urine samples of two volunteers after oral administration of 7.5 mg zopiclone were investigated. The S-(+)-enantiomers of zopiclone and its metabolites were always excreted in higher amounts than the R-(-)-enantiomers. With the same method the zopiclone enantiomers were quantified in saliva. Compared to high-performance liquid chromatography, the CE method is very fast and simple.

Azabicyclo Compounds↗
PubMed1993

Preparative and analytical separation of the zopiclone enantiomers and determination of their affinity to the benzodiazepine receptor binding site.

We report the preparative separation of rac-zopiclone using malic acid as the resolving agent. Furthermore, two different methods for the analytical determination of zopiclone enantiomers by HPLC on chiral stationary phases are described. The benzodiazepine receptor binding of the isolated enantiomers was investigated. Half-maximal inhibitory concentrations of (+)- and (-)-zopiclone were 21 or 1,130 nmol/liter, respectively, indicating a more than 50 times higher affinity of the (+)-enantiomer toward the receptor.

Animals↗
PubMed1990

Effects of beta-casomorphin derivatives on gastrointestinal transit in mice.

Some D-amino acid-substituted derivatives of beta-casomorphin (CM) were found to exhibit a special affinity to central opiate receptors. Concerning their affinity to peripheral opiate receptors our knowledge is still limited. The results of our experiments indicate that CM derivatives interfere with peripheral opiate receptors and that there is a close connection with the affinity to different subtypes of this receptor.

Amino Acid Sequence↗
PubMed1989

[Modern imaging procedures in the diagnosis of an acute apoplectic insult and their therapeutic consequences].

The acute occlusion of arteries as an acute condition demands immediate action. Previously the radiologist was only involved with the angiography elucidation but with the advent of hemolytic therapy a close cooperation of radiologist and intensive care physicians becomes necessary. Under intensive care conditions, the radiologist must be available around the clock, even at night and on holidays. First results of haemolytic therapy seem to justify these efforts.

Adult↗
PubMed1987

[Current therapy of chronic arterial occlusive diseases of the lower extremities].

Angiologists, vascular surgeons, and angiographers inform about the actual state of the therapy of the arterial occlusive diseases of the legs. The degree I of therapy comprises the conservative treatment for the improvement of the macrocirculation and the normalisation of the disturbed microcirculation, taking into particular consideration the therapy with antiviscositant drugs. The main chapter ends with the possibilities of the influence on the arteriosclerotic vascular processes as well as with the necessary rehabilitative measures. In the paragraph about the degree II of therapy the indications, contraindications, methods and results of the isolated and combined percutaneous transluminal angioplasty, the systemic and local fibrinolysis as well as the reconstructive vascular operations are represented.

Arterial Occlusive Diseases↗
PubMed1987

[Value of systemic streptokinase therapy in thromboembolism diseases].

Among 27,756 cases with stationary treatment 1,532 patients were found in whom a systemic fibrinolysis therapy was taken into consideration. Under strict attention to indications and contraindications 173 patients were treated with streptokinase. The rate of treatment failures in peripheral arterial obstructions was 46%, in venous thromboses 29%. The lethality of pulmonary embolisms could be decreased significantly, in acute myocardial infarction however, it could not be reduced. In 10% of the cases we observed severe therapeutic complications. The systemic streptokinase therapy is therefore a certainly effective, but also high-risk method of treatment, which must be performed by an experienced physician.

Humans↗