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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 298 (1977), S. 205-210 
    ISSN: 1432-1912
    Keywords: Synaptic transmission ; 14C-choline ; Acetylcholine ; Phosphatidylcholine ; Urethane anesthesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Concentrations and specific radioactivities of choline, acetylcholine, phosphorylcholine, lipid choline, and sn-glycero-3-phosphorylcholine after i.v. injection of methyl-14C-choline were measured in the brain of untreated controls and of rats anesthesized with urethane. The specific activity was found to be decreased during deep anesthesia by 40% in acetylcholine, 20–30% in phosphorylcholine, 50–75% in lipid choline, and 30–40% in sn-glycero-3-phosphorylcholine. No significant change was detected in the specific activity of choline. The brain concentration of acetylcholine was increased by 40%, the concentration of sn-glycero-3-phosphorylcholine, however, was diminished by 10% during anesthesia. No change was found in the concentration of the other choline containing compounds investigated. Measuring choline incorporation into 4 subcellular fractions of brain tissue specific activities were found to be decreased by the same percentage, although 2 fractions (nuclei and microsomes) were higher labelled than the 2 other fractions (crude mitochondria with synaptosomes and lysosomes). A correlation between the biochemical and the functional alterations is supported by the dose-effect relationships on both parameters. It is suggested that urethane reduces turnover of lipids and by that mechanism inhibits the exocytotic release of the transmitter from presynaptic nerve endings.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 28 (1985), S. 213-219 
    ISSN: 1432-1041
    Keywords: thiamine ; plasma level ; pharmacokinetics ; nonlinear renal elimination ; assay for clinical use
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A sensitive assay for thiamine suitable for clinical use has been developed. It is based on precolumn oxidation of thiamine to thiochrome followed by HPLC-separation and fluorescence detection. The assay is applicable to various biological materials, including human plasma. The minimum amount detectable was 5 fmol, minimum plasma concentration 0.5 nmol/l and minimum sample volume 0.3 ml plasma. Each chromatographic run took 3 min. Inter- and intra-assay relative standard deviations (RSD) were 8.3% and 6.3%, respectively, at a stock plasma concentration of 10.8 nmol/l. At 38.8 nmol/l, interassay RSD was reduced to 3.4%. The recovery of 5 nmol/l added thiamine was 102 (SD±17)%, that of 30 nmol/l was 94±5%. Plasma levels in 91 volunteers ranged from 6.6 to 43 nmol/l, showing a log normal distribution with a median of 11.6 nmol/l. Thiamine kinetics were studied in plasma and urine from 8 men after intravenous and oral doses of 50, 100 and 200 mg thiamine hydrochloride. In all individuals, nonlinear renal elimination kinetics were demonstrated by plotting the fractional amount of thiamine excreted unchanged in urine against the corresponding area under the plasma concentration — time curve.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Diabetes mellitus ; drug interaction ; phenprocoumon ; pharmacokinetics ; pharmacodynamics ; sulphonylureas
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of various antidiabetic treatments on the kinetics and efficacy of a single oral dose of 12 mg phenprocoumon were studied in 71 hospitalized patients, 58 with adult-onset diabetes mellitus and 13 non-diabetic aged patients, and 13 healthy young volunteers. Treatment for one week or longer with insulin or the antidiabetic sulphonylureas tolbutamide, glibenclamide or glibornuride, altered neither the plasma level (1.29 – 1.40 µg/ml at zero time) nor the half-life of phenprocoumon (5.2 – 6.8 d) compared to treatment by diet alone. The mean half-life of phenprocoumon was significantly shorter in non-diabetic aged patients (4.2 d) than in diabetic patients of the same age (5.1 – 6.8 d), or in young healthy volunteers (5.7 d). The efficacy of a single dose of phenprocoumon (maximal reduction of Quick-values by 34 – 47% after 48 to 72 hrs) in diabetic patients treated with diet, or diet and antidiabetic drugs, was the same as in non-diabetic aged patients. In healthy young volunteers phenprocoumon was half as effective as in aged patients.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 39 (1990), S. 603-605 
    ISSN: 1432-1041
    Keywords: Galanthamine ; Alzheimer's disease ; stereoselectivity ; cholinesterase inhibition ; side effects ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of galanthamine (GAL) and its 2 major metabolites on human cholinesterases has been explored. Epigalanthamine, a diastereomer of GAL, was 130-times less potent in vitro in its effect on acetylcholinesterase (AChE) in erythrocytes than the parent compound, and it did not differ significantly from the ketone galanthaminone. In vivo, the maximal 36–55% inhibition of AChE was approached 30 min after oral administration of 10 mg GAL. The duration of the catalytic inhibition corresponded to an elimination half-life of approximately 5–7 h. GAL was well tolerated in 8/8 healthy volunteers, and 3/4 Alzheimer patients tolerated the drug up to a daily dose of 40 mg.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 38 (1990), S. 237-242 
    ISSN: 1432-1041
    Keywords: cyclosporin A ; diltiazem ; pharmacokinetics ; kidney transplantation ; drug metabolism ; cytochrome P-450 ; drug interactions ; human liver microsomes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Previous reports have indicated that administration of the calcium antagonist diltiazem results in major changes in the pharmacokinetics of cyclosporin A (CyA). A new clinical trial was undertaken in 22 renal transplant patients receiving a constant dose of cyclosporin to further explore this interaction. Coadministration of diltiazem for one week produced an increase in the blood concentration of CyA and its metabolites 17 and 18 in almost all patients, but no increase in CyA metabolites 1 and 21. The mean whole blood CyA trough level determined by HPLC rose from 117 ng·ml−1 to 170 ng·ml−1 after one week on diltiazem, and the mean trough level of metabolite 17 rose similarly from 184 ng·ml−1 before to 336 ng·ml−1. Based on experiments with microsomes from human liver the effect of diltiazem was due to noncompetitve inhibition of CyA-metabolism by diltiazem, and the increased concentration of metabolite 17 might have been due to stronger inhibition of its secondary metabolism steps.
    Type of Medium: Electronic Resource
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