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  • 1
    Electronic Resource
    Electronic Resource
    Quantitative determination by HPLC of urinary 6β-hydroxycortisol, an indicator of enzyme induction by rifampicin and antiepileptic drugs (1979)
    Springer
    European journal of clinical pharmacology 16 (1979), S. 63-71 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00644969
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  • 2
    Electronic Resource
    Electronic Resource
    Kinetics of hexobarbital and dipyrone in critical care patients receiving high-dose pentobarbital (1987)
    Springer
    European journal of clinical pharmacology 32 (1987), S. 273-277 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00607575
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  • 3
    Electronic Resource
    Electronic Resource
    Pharmacokinetic interaction between cyclosporin and diltiazem (1990)
    Springer
    European journal of clinical pharmacology 38 (1990), S. 237-242 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00315023
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  • 4
    Electronic Resource
    Electronic Resource
    The kinetics of metamizol and its metabolites in critical-care patients with acute renal dysfunction (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 445-450 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00315516
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  • 5
    Electronic Resource
    Electronic Resource
    Stoichiometric cooperation of NADPH and hexobarbital in hepatic microsomes during the catalysis of hydrogen peroxide formation
    Amsterdam : Elsevier
    Archives of Biochemistry and Biophysics 216 (1982), S. 455-465 
    Details
    ISSN: 0003-9861
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1016/0003-9861(82)90234-X
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  • 6
    Electronic Resource
    Electronic Resource
    Clearance of ceftriaxone in critical care patients with acute renal failure (1990)
    Springer
    Intensive care medicine 16 (1990), S. 448-453 
    Details
    ISSN: 1432-1238
    Keywords: Ceftriaxone ; Pharmacokinetics ; Acute renal failure ; Intensive care patients
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Serum concentrations of ceftriaxone (RocephinTM), a third generation cephalosporin, were monitored in 5 operative intensive care patients suffering from acute renal failure (ARF) and compared to those of 7 patients without renal disturbance. For a period of 7 days, a fixed dose of 2 g/day was given by a 15 min infusion. Pharmacokinetic parameters were calculated by fitting all serum and urine data measured over the period of treatment. Ceftriaxone free fraction was measured on days 2 and 7. There was no evidence for an intraindividual change in ceftriaxone-clearance during the observation period. Ceftriaxone renal clearance was closely dependent on creatinine clearance according to a linear regression expressed by Clren=0.14 Clcrea+2.2 (r=0.951,p〈0.0001). Total clearance was also associated with creatinine clearance: Cltot=0.19 Clcrea+8.2 (r=0.964,p〈0.0001). Related to the free fraction, renal clearance was in the range of the glomerular filtration rate. Non-renal clearance was strongly decreased when related to the free fraction indicating that biliary excretion is also impaired in patients with acute renal failure. Obviously no compensatory increase in hepatic ceftriaxone clearance takes place. It is concluded that elimination of ceftriaxone may be strongly impaired during acute renal failure in surgical intensive care patients and that dosage should be restricted according to degree of the impairment of creatinine clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01711224
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  • 7
    Electronic Resource
    Electronic Resource
    Hybrid information provided by the 14C-aminopyrine breath test studies with 14C-monomethylaminoantipyrine in the guinea pig (1980)
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 313 (1980), S. 175-178 
    Details
    ISSN: 1432-1912
    Keywords: 14C-aminopyrine breath test ; 14C-monomethylaminoantipyrine ; Drug metabolism capacity ; guinea pig ; N-demethylation reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary N-Demethylation of 14C-aminopyrine (14C-AP), labelled at the methyl groups of the tertiary amino group, yields H14CHO and 14C-monomethylaminoantipyrine (14C-MMAAP) which also undergoes N-demethylation, however, at a slower rate as measured in hepatic microsomes. As after intraperitoneal application to male guinea pigs of 14C-AP (75 mg/kg; 50 μCi/kg), exhalation rate of 14CO2 declines in a biphasic manner, the hypothesis was tested whether the terminal part might reflect N-demethylation of MMAAP. The application of 14C-MMAAP (70 mg/kg; 10 μCi/kg), resulted in monophasic curves of 14CO2 exhalation rate. Their half lives were, however, longer than terminal half lives obtained after 14C-AP. Obviously, this terminal phase does not represent 14CO2 formation from the metabolite MMAAP only, but 14C-AP might still contribute to 14CO2 production. Confirmation was obtained by HPLC determination of AP and MMAAP in serum after injection of AP. Shortly after injection, high concentrations of AP and low ones of MMAAP were found in blood from the portal vein and systemic circulation. Thus, initial parts of 14CO2-exhalation rate curves reflect predominantly AP metabolism whereas later phases provide hybrid information.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00498577
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  • 8
    Electronic Resource
    Electronic Resource
    Erfassung von gesundheitlichen Störungen und Einschätzung toxischer Risiken durch chemische Produkte beim Menschen Die ärztlichen Mitteilungen bei Vergiftungen (§ 16e Chemikaliengesetz) als etabliertes gesetzliches Monitorsystem (2000)
    Springer
    Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz 43 (2000), S. 351-359 
    Details
    ISSN: 1437-1588
    Keywords: Schlüsselwörter Vergiftungen ; Humandaten ; Monitorsystem ; Toxikovigilanz ; Keywords Poisonings ; Human Data ; Monitoring system ; Toxicovigilance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary From 1st August 1990 onwards health complaints in connection with chemical product exposure were assessed by an official monitoring system. The reports of the primary care physicians are documented in a standardized form, assessed, evaluated and analysed. Results are reparted and recommendations for risk management are directed to the published. Beside the systematic documentation of human toxicological data in form of standard files and case-reports, the monitoring system has an important toxicovigilance function: Serious health effects from acute or chromic chemical product exposure are analysed immediately, all other health complaints from exposures annually and directed for risk-management to the producers, distributors, industrial associations and the government.
    Notes: Zusammenfassung Seit 1.8.1990 werden gesundheitliche Störungen im Zusammenhang mit chemischen Produkten mit Hilfe eines gesetzlichen Monitorsystems erfasst. Die Mitteilungen der behandelnden Ärzte werden standardisiert dokumentiert, bewertet und analysiert. Die Ergebnisse werden regelmäßig veröffentlicht. Neben der systematischen Dokumentation von toxikologischen Daten am Menschen durch Standarddatensätze und Einzelkasuistiken, hat das Monitorsystem eine besondere Leistungsfähigkeit durch eine Risikoidentifizierungs-/Toxikovigilanz-Funktion: Schwerwiegende Beeinträchtigungen der Gesundheit werden unmittelbar, alle übrigen einmal im Jahr analysiert und den Ministerien, Herstellern, Vertreibern und den Industrieverbänden zum Risikomanagement mitgeteilt-
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001030050265
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