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  • 1
    facet.materialart.
    Unknown
    German Medical Science; Düsseldorf, Köln
    In:  Kooperative Versorgung - Vernetzte Forschung - Ubiquitäre Information; 49. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 19. Jahrestagung der Schweizerischen Gesellschaft für Medizinische Informatik (SGMI) und Jahrestagung 2004 des Arbeitskreises Medizinische Informatik (ÖAKMI) der Österreichischen Computer Gesellschaft (OCG) und der Österreichischen Gesellschaft für Biomedizinische Technik (ÖGBMT); 20040926-20040930; Innsbruck; DOC04gmds134 /20040914/
    Publication Date: 2004-09-14
    Keywords: ddc: 610
    Language: English
    Type: conferenceObject
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  • 2
    facet.materialart.
    Unknown
    German Medical Science GMS Publishing House; Düsseldorf
    In:  81. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie; 20100512-20100516; Wiesbaden; DOC10hnod657 /20100422/
    Publication Date: 2010-04-23
    Keywords: ddc: 610
    Type: conferenceObject
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  • 3
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: 6beta-hydroxycortisol ; rifampicin ; cortisol metabolism ; high performance ; liquid chromatography ; urine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A method for determination of 6β-hydroxycortisol in urine by means of high performance liquid chromatography is described. After extraction of 10–30 ml aliquots of urine with ethylacetate, separation is accomplished on a silica gel column (30 cm, Lichrosorb Si 100) with a special two-phase four-component eluent of methylene chloride, n-hexane, ethanol and water. Complete separation of α- andβ-isomers requires 15 to 20 min. For routine determinations precolumn cleaning by backflush permits injections of samples at minimum time intervals. For quantitative determinations, each injection should contain at least 0.05–0.5 µg of 6β-hydroxycortisol, depending on the detector employed. The mean excretion rate in healthy male adults (26–40 years) was 273 µg/day (SD=74.5; n=12). In patients on long term mono-therapy with rifampicin, 6β-hydroxycortisol excretion had risen fourfold (1166 µg/d; SEM=248; n=7), paralleling the known enzyme-inducing effect of rifampicin. The relatively smaller increase to 498 µg/d observed in patients receiving triple therapy with rifampicin, isoniazid and ethambutol points to possible inhibition by isoniazid. The greatest stimulation of 6β-hydroxycortisol excretion (2352 µg/d) was found in patients receiving antiepileptic therapy (phenytoin and/or carbamazepine and other drugs). The HPLC technique for 6β-hydroxycortisol proved to be a tool routinely applicable to non-invasive evaluation of drug metabolizing enzyme activity in man.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1041
    Keywords: D-glucaric acid ; renal insufficiency ; phenobarbital ; dipyrone ; cortisol ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion rate ofD-glucaric acid, an in vivo parameter of the activity of drug metabolizing enzymes, has been determined in patients with chronic renal insufficiency (glomerular filtration rate 4.5–80 ml/min/1.73 m2). The mean value of 22.3 µmoles/d (SD 7.2; n 28) was almost identical to that of healthy controls (22.1 µmoles/d, SD 7.3; n 22). Thus, no inhibitory or enhancing effect of renal insufficiency could be detected. The ability of this parameter to indicate alterations in the activity of hepatic drug metabolism, even in patients with renal insufficiency, was demonstrated by the increased excretion rate of glucaric acid (107 µmoles/d, SD 43.5; n 8; p〈0.001) after treatment for 7 days with the enzyme inducer phenobarbital. No significant correlation was found between glucaric acid excretion and sex, age, body weight or body surface in 50 patients. Glucaric acid excretion, therefore, should not be related to the creatinine content of urine samples, since creatinine excretion decreases with severity of renal insufficiency and varies with sex, age, body weight and many other conditions. A single dose of dipyrone (Novalgin®), a further in vivo indicator of drug metabolism, increased glucaric acid excretion on the same day, but no interference was found after a single dose of cortisol.
    Type of Medium: Electronic Resource
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  • 6
    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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  • 7
    ISSN: 1432-1041
    Keywords: Metamizol ; Acute renal failure ; Sepsis ; intensive care patients ; drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have studied the clearance of monomethylaminoantipyrine (MMAAP), the pharmacologically active form of metamizol, in 46 patients in surgical intensive care with different degrees of renal dysfunction. In 23 patients without any renal impairment, mean clearance was 2.8 ml·min−1·kg−1. Twentyone patients with acute renal impairment had a significantly reduced clearance of MMAAP (0.83 ml·min−1·kg−1). There was also reduced clearance in four patients with septic shock (1.0 ml·min−1·kg−1). Kinetics of the metabolites of MMAAP (N-formylaminoantipyrine (FAAP), aminoantipyrine (AAP), and its secondary product N-acetylaminoantipyrine (AcAAP)) were calculated. FAAP and AcAAP showed delayed invasion, which can be explained by reduced hepatic metabolic activity. The product of N-demethylation, AAP, was not significantly altered. The delayed elimination of monomethylaminoantipyrine can be explained by reduced hepatic function in parallel with acute renal failure due to disturbed cardiovascular function caused by septic shock. This may also lead to disturbed hepatic macro- and microperfusion associated with altered oxygen supply and oxygen consumption.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-1041
    Keywords: Glucaric acid ; aminopyrine half life ; gamma-glutamyl-transpeptidase ; 6β-hydroxycortisol ; enzyme induction ; drug metabolism in man
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The 24 h urinary excretion of 6β-hydroxycortisol and D-glucaric acid, the plasma half-lives and total clearances of aminopyrine, and serum gamma-glutamyl-transpeptidase activity have been measured in nineteen healthy male volunteers. The study was done double blind and was conducted as a test of induction of microsomal drug metabolizing enzymes during and after daily doses of 6 mg clemastine, 300 mg phenobarbital or a placebo. The urinary excretion of 6β-hydroxycortisol and D-glucaric acid was significantly increased in the phenobarbital group, the standard for induction. No changes were observed after treatment with clemastine or placebo. Phenobarbital also reduced the half life of aminopyrine, but it was not affected by clemastine or placebo. Gamma-glutamyl-transpeptidase activity increased only in the phenobarbital group. The elimination constant k2 of aminopyrine and the excretion of glucaric acid in the pre-medication period were correlated (p〈0.05). The results indicate that the tests were of diagnostic value in determination of microsomal enzyme induction by phenobarbital. Failure to observe similar changes after treatment with clemastine imply failure of induction of this activity under the experimental conditions.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1041
    Keywords: antipyrine ; chronic renal failure ; drug metabolism ; metabolism ; cumulation ; renal excretion ; pharmacokinetics ; clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3-hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function. Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance. The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies.
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  • 10
    ISSN: 1432-1041
    Keywords: pentobarbital ; hexobarbital ; dipyrone ; intensive care ; D-glucaric acid ; pharmacokinetics ; drug interactions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of pentobarbital treatment in a mean dose of 30 mg/kg/day on the clearance of hexobarbital (Evipan) and dipyrone (Novalgin) has been evaluated in critical care patients receiving a large number of drugs as comedication. Eleven patients treated with pentobarbital showed a hexobarbital half-life of 2.79 h and a total plasma clearance of 9.80 ml·min−1·kg−1 as compared to 10 patients without pentobarbital administration in whom there was a significantly longer half life (6.92 h) and lower clearance (2.97 ml·min−1·kg−1). The kinetics of hexobarbital were correlated with the urinary excretion of D-glucaric acid, a non-invasive parameter of drug metabolising activity. In 10 patients on pentobarbital, the total plasma clearance of N-4-methylaminoantipyrine, the active form of dipyrone, did not differ from that in 8 patients not receiving pentobarbital. As drug kinetics show great variability in these patients, it is difficult to discriminate enzyme induction from other mechanisms, for example competitive inhibition or changes in volume of distribution. In the presence of pentobarbital, however, induction of drug metabolising enzymes should be considered as a possible reason for the higher clearance of hexobarbital.
    Type of Medium: Electronic Resource
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