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  • 1
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Small general purpose analog computers are not usually equipped for iterative computation. Since multiple dosage problems are often encountered in pharmacokinetic studies an approximating program is proposed for rapid estimation and curve fitting. The program produces an input function simulating a staircase by integration only of the positive differentials of a sequence of rectangular impulses. The program is used to compute the maximum and minimum concentration factors of Sparteine and Quinidine as examples of two substances obeying first order kinetics. It is apparent from the results that the choice of dosage schedules is restricted both by the pharmacological and the pharmacokinetic properties of the drugs.
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  • 2
    ISSN: 1432-1041
    Keywords: moxalactam ; antibiotic ; plasma level ; cerebrospinal fluid ; high performance liquid chromatography ; assay method
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary A sensitive and reproducible method for the measurement of moxalactam in plasma and cerebrospinal fluid is described. Plasma proteins were removed by precipitation with ice-cold methanol at pH 5.6 and centrifugation. The supernatant was analysed by HPLC on a µ-Bondapack/phenyl column, with a mobile phase of acetonitrile/water/PIC Reagent A (20/80/1), and detection at 280 nm. The calibration curve was linear for plasma concentrations from 10 µg/ml to 60 µg/ml. Reproducibility was 4.7% (coefficient of variation) for within-day analysis and 13.8% for day-to-day analysis. Plasma concentrations in 9 moxalactam-treated patients with severe infections ranged from 0.9 µg/ml to 409 µg/ml. Individual pharmacokinetic parameters were calculated using a personal computer. In selected cases moxalactam concentrations were also determined in cerebrospinal fluid and tracheal aspirates.
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  • 3
    ISSN: 1432-1041
    Keywords: Enteral absorption transfer ; transit ; occupancy ; availments ; multicompartment modell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The transfer of a drug from the compartment in which it is applied to one from which samples can be taken can be determined from time-concentration curves by simple graphical and numerical procedures. The method requires subdivision of the total transferable amount of the drug into four quantities — occupancy, transit, transfer and availment, which can be obtained by an extension of the rule of corresponding areas. Each of these quantities is represented by a fractional area under the experimental time-concentration curve. Subdivision into fractional areas is possible if an additional experiment is performed in which the drug is placed directly in the reference compartment from which the estimations are made. The principle of the method is explained, and its application is demonstrated in examples of the gastrointestinal absorption of iron in children.
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of pediatrics 108 (1970), S. 201-207 
    ISSN: 1432-1076
    Keywords: Elimination half Life ; Rate Constant of Elimination ; Distribution Volume ; Pool ; Transfer ; Transfer of Iron ; Transfer of Bilirubin ; Transfer of Glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Elimination körperfremder Substanzen folgt gewissen Gesetzmäßigkeiten, die es erlauben, Konzentrationsverlaufskurven z. B. nach rascher intravenöser Injektion derartiger Stoffe mathematisch auszuwerten. Es werden Daten über die Eliminationsgeschwindigkeit und über die Verteilung erhalten. Sie dienen zur Berechnung von Dosierung und Dosierungsintervallen und gehören damit zur Charakterisierung von Arzneimitteln. Andererseits wird mit bekannten Teststoffen die Größe von Flüssigkeitsräumen oder die exkretorische Leistungs-fähigkeit von Organen oder von Organsystemen bestimmt. Die gleichen Gesetzmäßigkeiten gelten auch für endogene Substanzen. Nach intravenöser Belastung ist die Kurve der Erhöhung über den Nüchternwert in gleicher Weise der Auswertung zugänglich. Sie liefert neben den Daten über das Verteilungsvolumen und die Eliminationsgeschwindigkeit noch Angaben über den leicht austauschbaren Pool, und über den endogenen Umsatz (Transfer). Modellversuche und vergleichende Untersuchungen mit der Tracertechnik beweisen die Übereinstimmung der mit dieser Methode ermittelten Daten mit den tatsächlichen Umsatzgrößen. Drei Beispiele sollen die Bedeutung der Untersuchung endogener Substanzen mit pharmakokinetischen Methoden darstellen: Ikterus (Bilirubin), Anämie (Eisen) und Hypoglykämie (Glucose).
    Notes: Abstract The elimination of foreign substances is subject to rules which allow a mathematical interpretation of the course of the concentration. The results yield data on the rate of elimination and the distribution volume and make it possible to estimate the dosage and the intervals of dosage; this information can therefore be used for the characterisation of drugs. On the other hand, suitable test substances are used to estimate the size of fluid spaces and the excretory efficiency of organs and organ systems. Endogenous substances are subject to the same rules. The excess curve after intravenous administration allows a similar interpretation. Apart from data on the distribution volume and the rate of elimination, it yields information on the easily exchangeable pool and on endogenous transfer. Model tests and comparative tests using the tracer technique demonstrate that the data obtained by this method agree with the true value of the transfer. Three examples emphasize the importance of the examination of endogenous substances with pharmaco-kinetic methods: jaundice (bilirubin), anaemia (iron), and hypoglycemia (glucose).
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  • 5
    ISSN: 1432-1041
    Keywords: Pharmacokinetics ; curve fitting program ; desk computer ; Gauss-Newton ; non-linear least squares fitting
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Therotatingiterativeprocedure (RIP) is a programming concept for non-linear least squares fitting of multiexponential equations to experimental data in pharmacokinetics. The method is economical in its use of program and active register capacity and can be employed in modern electronic desk-top computers. The algorithms necessary for obtaining primary estimates of various logarithmic components and their subsequent correction are presented, with as little higher mathematics as appeared permissible. The procedure is described in the sequence that would actually be followed in a pharmacokinetic analysis, and an example is included, as well as a skeleton version of a program written in BASIC. Some instructions for obtaining overall statistical parameters are given.
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  • 6
    ISSN: 1432-1076
    Keywords: Oxygen Saturation ; Capillary Blood Method ; Cyanosis ; Congenital Heart Disease ; Intensive Care
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die arterielle O2-Sättigung ist in der Pädiatrie eine wichtige Meßgröße geworden. Ihre wiederholte Bestimmung nach Arterienpunktion ist im Säuglings- und Kleinkindesalter oft nicht möglich. Es wurde ein Meßgerät geprüft (OSM 1 der Fa. Radiometer, Copenhagen), das die Bestimmung der O2-Sättigung im Capillarblut ermöglicht, welches durch Stichincision gewonnen wird. Diese Methode hält den statistischen Prüfungen unter den Einsatzbedingungen eines pädiatrischen Krankengutes stand. Die Messungen sind auch bei Neugeborenen und cyanotischen Kindern (z. B. bei angeborenen Herzfehlern) genügend genau, wenn bestimmte Voraussetzungen beachtet werden. Die sichere Verwertbarkeit der Meßwerte für die capilläre O2-Sättigung ist nicht mehr gegeben, wenn der Blutfluß an der Stichincision schlecht ist und wenn das Kind stark schreit. Der Vergleich zwischen hämoreflektometrisch und mit der Capillarmethode bestimmten O2-Sättigungswerten ist auch dann gut, wenn zum Zwecke der Verlaufskontrolle 1–2 Tage zwischen den Vergleichsmessungen liegen. Der Einsatz des Gerätes eignet sich besonders in der pädiatrischen Kardiologie und Intensivpflege.
    Notes: Abstract Arterial oxygen saturation is now one of the important values in paediatrics. It is not always possible to perform repeated estimations in infants and children after puncture of an artery. An apparatus that renders the determination of oxygen saturation of capillary blood possible is tested. The blood specimen is gained by prick incisions. These methods stand the statistical tests under the conditions applicable in paediatric cases. The values are also sufficiently accurate in neonates and cyanosed children (e.g. congenital heart diseases) when certain conditions are taken into consideration. If the circulation at the site of the prick incision is poor and if the child screams vigorously, the value of the capillary oxygen saturation thus gained is not reliable. A comparison between the oxygen saturation values gained by the capillary and hemoreflectometer methods is also statistically valid, if 1 day or 2 lie between the tests. The apparatus is especially suitable in paediatric cardiology and intensive care.
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  • 7
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary A method for fluorometric estimation of micro-amounts of calcium (about 10 nEq./sample) in biological materials using calcein as indicator. Its applicability to heart muscle specimens (6–100 mg wet weight) and its limitation by interfering substances are described.
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  • 8
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary By means of a highly sensitive fluorometric method for the estimation of calcium in biological materials, the molecular sieving properties of Sephadex G-25 are used in a batch test to evaluate the concentration of non protein bound calcium in serum. The method can be applied to serum samples of one milliliter without appreciable interference with the mass law equilibrium. To demonstrate the reliability of the method the changes in the protein free fraction of calcium in serum elicited by pH variations are described.
    Notes: Zusammenfassung Der Molekülsiebeffekt hochvernetzter Dextrane (Sephadex) wird zur Trennung des an Eiweiß gebundenen Anteils von Serumcalcium vom frei diffusiblen Calcium verwendet. In Verbindung mit einer sehr empfindlichen fluorometrischen Calciumbestimmungsmethode kann Sephadex zur Messung der frei diffusiblen Calciumfraktion in kleinen Serumproben (ca. 1 ml) verwendet werden, ohne daß das Dissoziationsgleichgewicht in der Probe wesentlich gestört wird. Zur Prüfung der Zuverlässigkeit der Methode wurde die Abhängigkeit des frei diffusiblen Anteils am gesamten Serumcalcium von der H+-Ionenkonzentration untersucht.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 51 (1973), S. 615-619 
    ISSN: 1432-1440
    Keywords: Water turnover ; elimination of water ; water load ; oral ; water load intravenous ; elimination of water in relation to age ; Volhard's water loading ; Wasserumsatz ; Wasserelimination ; Wasserbelastung oral ; Wasserbelastung intravenös ; Altersabhängigkeit der Wasserelimination ; Volhardscher Wasserversuch
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Durch entsprechende Auswertung einer Wasserbelastung im Sinne des Volhardschen Wasserversuchs läßt sich nach den Vorstellungen und Experimenten von Ther und von Dost die Umsatzgeschwindigkeit des Wassers ermitteln. 159 Kinder wurden einer oralen oder z.T. wiederholten i.v. Wasserbelastung unterzogen. 15 Doppelbelastungen zeigten, daß die Reproduzierbarkeit ausgezeichnet ist. Gesunde Kinder zeigten vom 12. Lebenstage bis zu 15 Jahren im Mittel eine Eliminationshalbwertzeit von 40,6 min (0,68 h) bzw. eine Eliminationskonstante von 1,02 h−1. Bei jüngeren Kindern erfolgte die Elimination deutlich langsamer (t 50%=2,2 h,k 2=0,34 h−1). Bei verschiedenen krankhaften Zuständen war die Wasserelimination deutlich verlangsamt. Es wird festgestellt, daß mit Hilfe der pharmakokinetischen Auswertung der einfachen Wasserbelastung Daten über den biokinetischen Umsatz des Wassers gewonnen werden können.
    Notes: Summary The experiments of Ther and of Dost showed that Volhard's water load can be interpreted as to yield the rate of transfer of water through the body. Oral or intravenous water loading tests were performed in 159 children. Replications in 15 children showed excellent reproducibility. Healthy children twelve days to fifteen years of age have an elimination half life of water of5 50%=40.6 min (0.68 h) corresponding to a rate constant of elimination ofk 2=1.02 h−1. In various diseases a reduction of the rate of elimination can be observed. Our experiments demonstrate that it is possible to obtain biokinetical data on water turnover from the pharmacokinetical evaluation of Volhard's water load.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 47 (1969), S. 909-912 
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The intravenous glucose tolerance test yields the biokinetic standard parameters when analysed according to the pharmacokinetic principles. 31 children with ketonuria were investigated and the results were compared to those obtained from 68 healthy children. It was found, that the transfer of glucose is diminished in ketonuria. It is shown, that this diminution is not due to lack of glucose but to a low turnover constant combined with an impaired glucose-mobilisation. The application of large amounts of glucose leads to an increased glucose pool and thus to an increase of the transfer. This effect ist exaggerated by insulin. It is therefore suggested, that the non-diabetic hyperketonemic coma be treated with glucose infusions and insulin.
    Notes: Zusammenfassung Die mit der intravenösen Glucosebelastung gewonnenen biokinetischen Stoffwechselstandardgrößen von 31 Kindern mit Acetonurie werden mit denen von 68 gesunden Kindern verglichen. Es wird gezeigt, daß der Glucosedurchfluß durch das Blut (Transfer) bei Acetonurie vermindert ist und daß diese Verminderung nicht, wie vielfach angenommen wird, auf Glucosemangel beruht. Sie beruht vielmehr auf einer Herabsetzung des Glucoseverbrauchs bei gleichzeitiger Minderung der Glucoseneubildung. Die Zufuhr großer Glucosemengen bewirkt eine Vergrößerung des leicht austauschbaren Pool und damit eine Steigerung des Transfer. Dieser Effekt kann durch die Gabe von Insulin weiterhin verstärkt werden. Die Behandlung des nichtdiabetischen hyperketonämischen Komas mit Glucose und Insulin wird deshalb vorgeschlagen.
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