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  • 1
    ISSN: 1432-0711
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 1. Cephacetril1, ein neues Cephalosporinderivat wurde gesunden Schwangeren während der Geburt durch eine Dauerinfusion mit einer Infusionspumpe (Dosis 0,5 g/Std) und durch intravenöse Einzelinjektionen von 1 g zweistündlich appliziert. Mütterliche Serum- und Fruchtwasserkonzentrationen wurden wiederholt während der Geburt, mütterliche Serum- und Nabelschnurkonzentrationen nach der Geburt bestimmt. 2. Im mütterlichen Serum wurde durch die Dauerinfusion ein „steady state“ von 30 mcg/ml und durch wiederholte intravenöse Einzelinjektionen Schwankungen von maximal 65,1–90,8 mcg/ml und minimal 8,0–12,9 mcg/ml erreicht. 3. Die Nabelschnur- und Fruchtwasserkonzentration erreichten ungefähr 14 mcg/ml bzw. 8–9 mcg/ml bei der Dauerinfusion und 19 mcg/ml bzw. 22–25 mcg je ml bei den wiederholten Einzelinjektionen. Die zeitabhängigen Verteilungsquotienten und die Korrelationen zwischen den verschiedenen Konzentrationen wurden bestimmt. 4. Die intrauterinen Spiegel genügen, um gram-positive und den größten Teil der gram-negativen Erreger von intrauterinen Infektionen zu hemmen oder abzutöten. 5. Als Schlußfolgerung ergab sich, daß bei Patienten mit normaler Nierenfunktion eine hohe Dosierung von 12 g/24 Std des Antibioticums zur Behandlung und Prophylaxe intrauteriner Infektionen am Ende der Schwangerschaft oder während der Geburt zu empfehlen sind. Wiederholte intravenöse Einzelinjektionen scheinen höhere Fruchtwasser- und Nabelschnurkonzentrationen zu geben als dieselbe Menge des Antibioticums in einer Dauerinfusion.
    Notes: Summary 1. Cephacetrile1, a new cephalosporin analogue, was administered to healthy pregnant women during labor by continuous intravenous automatic infusions of 0.5 g/h or by intravenous injections of 1 g every two hours. Maternal serum and amniotic fluid concentrations were repeatedly determined during labor and maternal serum and cord serum concentrations after delivery. 2. In the maternal serum a steady state of 30μg/ml was obtained by continuous infusion and peaks with a maximum range of 65.1–90.8μg/ml and a minimum range of 8.0–12.9μg/ml by repeated intravenous injections. 3. Cord serum and amniotic fluid concentrations reached approximately 14μg/ml and 8–9μg/ml respectively in the continuous infusion group and 19μg/ml and 22–25μg/ml respectively in the repeated injection group. Distribution ratio and correlations between the various levels were determined. 4. The intra-uterine levels are adequate to inhibit or kill Gram-positive and the major part of Gram-negative pathogens of intra-uterine infections. 5. In conclusion, in patients with normal renal function high dose regimes of 12 g/24 h of the antibiotic are recommended for treatment or prevention of intra-uterine infections near term or during labor. Repeated single intravenous injections seem to give higher amniotic fluid and cord serum concentrations than the continuous infusion of the same amount of the antibiotic.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Inflammation research 7 (1977), S. 369-377 
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Kinetic analysis of minocycline concentrations in plasma and urine resulted in the following findings: In normal subjects the biological half-life is about 17 hours after the first dose and 21 hours after repeated administration. The renal drug clearance is only about 8% of the over-all plasma clearance which is independent of renal function with a mean value of 47 ml/min. The fraction of the absorbed dose eliminated unchanged in the urine is only 9–19%. As a consequence the elimination rate of the drug is practically independent of renal function and decreases only 9–19% in anuric patients. The renal drug clearance depends linearly on renal function. The gastro-intestinal bio-availability of minocycline from the coated tablet preparation is incomplete. The cumulative behaviour of the drug corresponds to the kinetic parameters determined after repeated administration. It is suggested that the usual dosage regimen should be used in patients with renal disease.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular life sciences 10 (1954), S. 230-231 
    ISSN: 1420-9071
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 274 (1961), S. 90-90 
    ISSN: 1432-2013
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 44 (1993), S. 271-274 
    ISSN: 1432-1041
    Keywords: Chloroquine ; Malaria ; prophylaxis schedules ; side effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Two antimalarial prophylactic regimens were compared in healthy subjects belonging to the flying personnel of Scandinavian Airlines System. Regimen I: 310 mg chloroquine (CQ) base was given once weekly, starting the week prior to departure to the endemic area, then weekly during presence there and for four weeks after return. Regimen II: a loading dose of 620 mg chloroquine base was given at the latest 48 h prior to departure to the endemic area, followed by 310 mg base weekly throughout the visit. Blood samples were analysed by HPLC for CQ and its major metabolite desethylchloroquine (CQM). Regimen I gave suboptimal whole blood concentrations of CQ and CQM at the end of the first week of treatment. Regimen II gave prophylactic concentrations from the beginning of visit up to 6 weeks after departure from the endemic area. Both regimens were well tolerated, but Regimen II appeared better accepted by the volunteers due to its shorter duration.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 5 (1972), S. 34-36 
    ISSN: 1432-1041
    Keywords: Digoxin ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The protein binding of digoxin in human serum was investigated using equilibrium dialysis and tritium-labelled digoxin. A constant protein bound fraction of about 30% was found over a wide range of concentrations of digoxin including therapeutic levels. Interpretation of the findings according to the law of mass-action showed an association constantK = 0.68·10−5l/mol; and, the number of binding sites,n → ∞, indicating an almost infinite apparent maximum binding capacity and a very small affinity of human serum proteins for digoxin.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 35 (1988), S. 1-7 
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 595-602 
    ISSN: 1432-1041
    Keywords: alcohol-kinetic study ; average parameter estimates (APE) ; individual parameter estimates (IPE) ; statistical method ; pharmacokinetic data
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The problems of obtaining optimal average parameter estimates (APE) from experimental pharmacokinetic data are considered. Four different approaches, three parametric and one non-parametric tests, are compared, using selected individual alcohol concentration data. Pooling the raw data for estimating APE can obscure individual pharmacokinetic characteristics, whereas averaging individual parameter estimates (IPE) exposes unique statistical problems. Furthermore, careful consideration should be given to weighting procedures. The advantages and shortcomings of all four methods are discussed. It is concluded that none can be considered as a universally applicable statistical method in view of the purpose for which the information, derived from a set of data, e.g. an alcohol-kinetic study, is required.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 619-626 
    ISSN: 1432-1041
    Keywords: ethanol kinetics ; concentration-time profile ; human volunteers ; oral administration ; breath alcohol ; blood alcohol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The concentration-time profile of ethanol in breath air (AAC), arterial (ABAC) and venous blood (VBAC) of human volunteers was studied after four different oral doses of absolute alcohol — 0.5, 0.75, 1.0, and 1.25 g/kg body weight. Seventy-eight single dose experiments were carried out in 42 subjects. In all 78 studies AAC was measured and VBAC was estimated simultaneously in blood collected from a cubital vein of 36 volunteers. Arterial blood, too, was collected from 8 subjects from a catheter in a brachial artery. All blood alcohol concentrations were analysed independently by gas chromatography (GLC) and an enzymatic (ADH) method. A one-compartment open model with first order absorption and pseudo-zero-order elimination was employed to calculate the pharmacokinetic parameters. The average values for the first order absorption rate constant (ka) ranged from 2.2 to 3.1, from 2.4 to 2.6 and from 1.0 to 1.7 h−1 for AAC, ABAC and VBAC, respectively. The pseudo-zero-order elimination rate constant (β) was 0.17 to 0.18, 0.21 to 0.22 and 0.26 to 0.27 g × 1−1 × h−1, respectively. During absorption ABAC tended to be higher than VBAC, peaking at a higher level (Cmax) and with a shorter time to peak (tmax) until an arterio-venous concentration equilibrium was reached, whereafter VBAC remained above ABAC. Although there was a close relationship between AAC, ABAC and VBAC during elimination, AAC closely followed the pattern of ABAC during absorption and tended to deviate from VBAC. AAC, therefore, is a much better predictor of ABAC during absorption than VBAC.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 1 (1968), S. 47-53 
    ISSN: 1432-1041
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Zusammenfassung Die Pharmakokinetik von Sulfisomidin und von Sulfisoxazol wurde bei 52 Kindern im Alter zwischen 5 and 357 Tagen untersucht. Dosen zwisehen 50 and 100 mg/kg Körpergewicht wurden peroral oder intravenös appliziert. Aus den Konzentrationswerten im Serum wurden mit Hilfe eines programmgesteuerten Digitalrechners die folgenden pharmakokinetischen Konstanten ermittelt: Die gastrointestinale Invasionskonstante, das relative Verteilungsvolumen und die Eliminationshalbwertszeit. Eine Eliminationskinetik erster Ordnung konnte in allen Fällen nachgewiesen werden. Für die Geschwindigkeitskonstanten der gastrointestinalen Absorption wurden hohe Werte gefunden, nämlich 0.95 h−1 für Sulfisomidin and 0.99 h−1 für Sulfisoxazol. Zwischen dem 5. und 9. Lebenstag war die Eliminationshalbwertszeit etwa doppelt so lang wie beim Erwachsenen. Mit zunehmendem Alter der Kinder fand sick eine kontinuierliche Zunahme der Eliminationsgeschwindigkeit. Diese war bei beiden Sulfonamiden am Ende des ersten Lebensjahres etwa doppelt so groß wie beim Erwachsenen. Demgegenüber war mit zunehmendem Alter nur eine mäßige Abnahme des relativen Verteilungsvolumens festzustellen. Aus diesen Befunden muß auf eine betrachtliche Zunahme der totalen Clearance dieser Sulfonamide während des ersten Lebensjahres geschlossen werden. Diese Zunahme ist von einem derartigen Ausmaß, daß sie durch einen Reifungsprozeß arzneimittelmetabolisierender Enzyme nicht erklärt werden kann. Aufgrund der Ergebnisse früherer Experimente besteht die Möglichkeit, daß die altersabhängigen kinetischen Unterschiede durch altersabhängige Unterschiede im Wachzustand der Kinder bedingt sind.
    Notes: Summary The pharmacokinetics of sulfisomidine and of sulfisoxazole was investigated in 52 infants. The age varied between 5 and 357 days. Doses between 50 and 100 mg/kg body weight of the sulfonamides were administrated intravenously and per os. From the concentration values in the serum the following constants were calculated by means of a digital computer: The velocity constant of absorption according to Diller, the relative distribution volume and the biological half-life according to Dost and Krüger-Thiemer. First-order elimination kinetics could be demonstrated in all cases. The values found for the gastro-intestinal absorption constant of sulfisomidine and of sulfisoxazole were 0.95 h−1 and 0.99 h−1, respectively, indicating a high speed of absorption. Between the 5th and the 9th day of life the biological half-lives of both sulfonamides were about twice as long as compared with the values reported in adults. From then on the speed of elimination increased with increasing age. At the end of the first year the elimination was about twice as fast as compared with the adult. The relative distribution volume decreased to a much lesser degree with increasing age. Consequently, a considerable increase of the total clearance of the sulfonamides during the first year of life must be postulated. The age-dependent kinetic differences are of such a magnitude that they can not be explained by the postnatal development of the drug metabolizing enzymes. It is postulated on the basis of the results of earlier experiments that the differences are caused by age-dependent differences in the state of walkfulness.
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