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All Library Books, journals and Electronic Records Telegrafenberg

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  • 1
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The influence of the jejunal bloodflow on the absorption of theophylline was investigated. The bloodflow through a segment under investigation was varied by changing the systemic blood pressure by means of a donor blood infusion into the jugular vein or by an infusion of isoprenaline or levarterenol into a femoral vein, and was measured by collecting the venous outflow from the intestinal segment. Above a bloodflow of approximately 0.40 µl/min/cm the flux/ flow ratio is reduced, and it is proposed that above this flow the intestinal epithelium provides the rate limiting step in the absorption of theophylline. When the bloodflow was held low for a prolonged time, the flux of theophylline decreased. The absorptive site bloodflow was calculated to be 18 % of the total bloodflow through the segment under investigation.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract N-(p-Chlorobenzoyl)-sulfamate was observed to produce potent hypolipidemic activity in rodents at 10 to 60 mg/kg/day. Liver phosphatidate phosphohydrolase and sn-glycerol-3-phosphate acyl transferase activities were suppressed by the agent in vitro and in vivo, and ATP dependent citrate lyase and acetyl CoA carboxylase activities were reduced in vivo. N-(p-Chlorobenzoyl)-sulfamate reduced cholesterol, neutral lipids, and triglycerides in the liver and increased excretion of cholesterol and neutral lipids in the bile and feces. Drug treatment reduced the neutral lipid and triglyceride content of serum chylomicrons, VLDL and LDL, and cholesterol content was reduced in the chylomicron and HDL fractions.
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  • 3
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The pharmacokinetic disposition of the anthracyclines, adriamycin (doxorubicin), daunorubicin, 4′-epi-adriamycin, carminomycin, and 4-demethoxy-daunorubicin, and the formation of their reduced C13 hydroxy metabolites were studied in dogs. The presence of a C14hydroxy group (adriamycin and 4′epi-adriamycin) drastically reduces the appearance of the C13 hydroxy metabolites in plasma. Substitution of the C4-H with C4-OH and C4-OCH3, in this rank order, decreases the area under the plasma concentration-time curves of the parent compounds and their C13 hydroxy metabolites.
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  • 4
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new method employing the principle of superimposition was developed to aid in the formulation of sustained-release dosage forms. Independently absorbed components of a product, e.g., waxed pellets for an oral capsule, are administered separately and their plasma level-time profiles determined. Using a trial and error procedure, the ratios of pellets are varied to obtain a desired plasma level-time profile. The use of (1) time averaged plasma concentration-time data, (2) amount remaining to be absorbed (excreted) plots, and (3) cumulative amount absorbed (excreted) plots were all shown to be inappropriate for pharmacokinetic analyses in general, and evaluation of sustained-release products in particular. It was recommended that raw plasma concentration-time data be made available for sustained-released products, and that individual rate of absorption plots be used to assess absorption kinetics. It was concluded that much of the sustained-release pharmacokinetic data presently in the literature have been presented in such a manner, e.g. averaged data, as to be of limited value.
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 1 (1984), S. 101-101 
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 1 (1984), S. 102-105 
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract It is an axiom of pharmacodynamics that drug effects are determined by drug concentration at the site of action. The link between concentration and effect can often be described by empirical models, but the ability to measure binding to the target tissue permits a more detailed description. The action and interaction of drugs at identifiable receptor sites can then be predicted from a knowledge of their binding properties and the law of mass action. The time course of drug effect is determined not only by drug disposition reflected in the blood circulation but also by the equilibration rate between blood and the effect site, and the steps linking the direct actions of the drug to their expression as an observable drug effect. Models encompassing these phenomena have been developed and have been applied in many situations to describe the kinetics of pharmacological response.
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  • 7
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new and efficient in vitro assay for evaluating reactivators of organophosphate-inhibited acetylcholinesterase has been developed. Low density polyethylene beads (4 mm) were func-tionalized to terminal aldehydes and used to immobilize acetylcholinesterase (AChE, Electrophorus electricus, E.G. 3.1.1.7) via a stable Schiff base link. AChE activity in columns containing immobilized enzyme could be continuously monitored spectrophotometrically in a closed loop flow system using acetylthiocholine and 5,5′-dithiobis(2-nitrobenzoic acid) (DTNB). Immobilized enzyme exhibited good esterase activity (0.5 units/bead), which could be retained on storage at −16°C for four months. The kinetics for substrate hydrolysis were flow-rate dependent below substrate saturation levels. This system allowed for independent inhibition and reactivation of the enzyme. Immobilized enzyme could be inhibited with diisopropylfluorophosphate (DFP) and 20–90% of original activity restored with several oximes in less than 20 minutes. The extent of reactivation was dependent on the concentration of the reactivators. This system has advantages over previously reported procedures, because hydrolysis of substrate due to reactivator is minimized and inhibitor-reactivator interactions are eliminated, subsequently minimizing the need to correct experimental results.
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  • 8
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The contribution of structural free space to the solvent power of water was examined by a systematic modification of the geometric factor. Gaps and holes, available to foreign molecule occupation, are thought to be filled at low concentrations (max. 1 %) of aliphatic alcohols. The effect upon solvency reached approximately 10%, which suggests that spatial parameters affect solvent power. The results demonstrate the importance of solvent purity in the dissolution process.
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  • 9
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The outer layer of the epidermis or stratum corneum is the major barrier to percutaneous absorption. It has been shown that there are numerous enzyme systems beneath the stratum corneum in the viable epidermis capable of metabolizing drugs. A number of prodrug and soft drug topical therapeutic agents have been designed. After these agents penetrate the stratum corneum, they are metabolized by the cutaneous esterase systems to the desired metabolites.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pharmaceutical research 1 (1984), S. 141-148 
    ISSN: 1573-904X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Compounds containing a terminal carbon-carbon triple bond, ranging in structure from the 17α-ethynyl substituted contraceptive steroids to acetylene gas, when administered to rats cause a selective and rapid time dependent loss of up to 50% of hepatic cytochrome P-450. Cytochrome b5 is not affected. Metabolic activation of the acetylenic substituent by the phenobarbital inducible, NADPH dependent, mixed function oxidases results in the formation of a reactive species which alkylates one of the tetrapyrrole nitrogen atoms of heme to form a 1 : 1 covalent adduct. Either cytochrome P-450 destruction or the formation of N-alkylated porphyrins (green pigments) have been used to assess factors affecting the extent of metabolic activation of the acetylenic group in rats, man, and other laboratory species. The chemical identity of a number of green pigments have been resolved. Those formed from 1-octyne consist of the protoporphyrin IX ring of heme substituted with the saturated 2-oxo-octyl group. In contrast, reactive metabolites of 1-octyne trapped with N-acetylcysteine contain the unsaturated 3-oxo-octenyl substituent. Two independent routes of activation of terminal acetylenes have been described to account for these results. Both pathways can lead to cytochrome P-450 loss but only one, probably involving an oxirene intermediate, leads to green pigment formation.
    Type of Medium: Electronic Resource
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