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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Calcified tissue international 2 (1968), S. 67-76 
    ISSN: 1432-0827
    Keywords: Calcergy ; Calciphylaxis ; Calcium ; Metals
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Description / Table of Contents: Résumé Chez le rat, des expériences ont montré que, sauf de rares exceptions, les calcifications produites au site d'injection d'acétate de plomb, de chlorure de cérium, chlorure de calcium ou de permanganate de potassium sont complètement prévenues ou fortement inhibées par l'application locale simultanée de provocateurs calciphylactiques, mais non par des agents non provocateurs. Malgré quelques exceptions (attribuées à des interrelations chimiques spécifiques entre certaines des substances utilisées), cette curieuse corrélation entre l'efficacité calciphylactique provocatrice et le pouvoir anticalcergique est, d'après le test χ2, hautement significative (P〈0,001).
    Abstract: Zusammenfassung Nach subcutaner Injektion von Bleiacetat, Ceriumchlorid, Calciumchlorid oder Kaliumpermanganat tritt an der Injektionsstelle eine starke Verkalkung auf. Bis auf sehr wenige Ausnahmen kann diese durch gleichzeitige lokale Anwendung von calciphylaktischen Provokatoren verhütet oder weitgehend unterdrückt werden. In dieser Beziehung sind nicht provolatorisch wirkende Stoffe inaktiv. Trotz der wenigen Ausnahmen (die wahrscheinlich auf spezifische, chemische Wechselwirkungen zwischen manchen der untersuchten Substanzen beruhen) ist dieser merkwürdige Zusammenhang zwischen calciphylaktisch provozierender und anticalcergischer Aktivität, nach dem χ2-Test berechnet, statistisch hochsignifikant (P〈0,001).
    Notes: Abstract Experiments on rats indicate that, with very few exceptions, the calcification which occurs at subcutaneous sites of treatment with lead acetate, cerium chloride, calcium chloride or potassium permanganate is completely blocked or severely inhibited by simultaneous topical application of calciphylactic challengers but not of non-challengers. Despite the few exceptions (which are thought to depend upon specific chemical interactions between some of the compounds tested) this singular correlation between calciphylactic challenging and anticalcergic potency, is highly significant by the Chi-square-test (P〈0.001).
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 22 (1982), S. 85-90 
    ISSN: 1432-1041
    Keywords: lignocaine ; verapamil ; propranolol ; bioavailability ; predictions ; first pass effect ; oral clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary For drugs with a high hepatic clearance, bioavailability is low due to the so-called “first pass effect”. Prediction of the bioavailability for these drugs has been only lossely tested. It is proposed that by plotting the reciprocal of bioavailability versus the oral clearance, a straight line with intercept of unity and slope of reciprocal of hepatic blood flow should ensue. For lignocaine and verapamil, this relationship was found to be strong and gave good predictability, whereas for propranolol this relationship was weak and gave poor predictability. The proposed method may be of value in determining whether the low bioavailability of a drug is due to hepatic first pass metabolism.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: verapamil ; pharmacokinetics ; bioavailability ; hepatic first-pass metabolism ; stable isotopes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Following i. v. administration, the plasma concentration-time curve of verapamil could best be described by either a mono- or biexponential equation. Total plasma clearance (1.26 l/min) approached liver blood flow (1.5 l/min), so it can be concluded that its clearance is liver blood flow-dependent. Although absorption was almost complete after oral administration, absolute bioavailability (20%) was low, due to extensive hepatic first-pass metabolism. The approach using stable isotope-labelled and unlabelled drug permits simultaneous administration by the intravascular and extravascular routes, thus allowing determination of absolute bioavailability in a single experiment.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 19 (1981), S. 343-347 
    ISSN: 1432-1041
    Keywords: cimetidine ; phenobarbital ; gastro-intestinal absorption ; bioavailability ; renal clearance ; non-renal clearance ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of orally administered cimetidine was studied in 8 healthy subjects before and after 3 weeks of treatment with phenobarbital 100 mg daily, and in a separate study 4 subjects received cimetidine intravenously before and after the administration of phenobarbital. There was no change in the volume of distribution, but total plasma clearance was increased by a mean of 18%, mainly due to a 37% increase in nonrenal clearance. Renal clearance and half-life were not significantly altered. The area under the plasma concentration-time curve after oral administration was significantly (P≪0.05) reduced by a mean of 15% after phenobarbital treatment. The amount of cimetidine excreted in urine and its sulphoxide metabolite were significantly (P〈0.05) reduced, on average by 34% and 26%, respectively by phenobarbital treatment. The data indicate that an apparent 20% reduction in the absorption of cimetidine was due to induction of gastrointestinal metabolism of cimetidine, with some contribution also from hepatic metabolism. Reduced absorption per se could not be totally excluded. Although the magnitude of the change was small, the finding of an 11% decrease in the time to achieve an effective plasma level of cimetidine after phenobarbital treatment may contribute to the ineffectiveness of cimetidine in certain patients.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 20 (1981), S. 225-228 
    ISSN: 1432-1041
    Keywords: cimetidine ; antacids ; metoclopramide ; absorption ; bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In 8 healthy subjects the absorption of cimetidine was investigated when given alone, together with 60 ml aluminium/magnesium hyroxyde containing antacid (neutralising capacity 26 mmol HCl/10 ml), and together with liquid metoclopramide 14 mg. The antacid significantly (P〈0.01) reduced the bioavailability (area under the plasma level-time curve) of cimetidine, on average by one third. Metoclopramide also reduced the bioavailability by an average of 22%. The reductions were associated with significantly reduced excretion of cimetidine in urine. There was no change in the half-life or renal clearance of cimetidine, supporting the hypothesis of reduced gastrointestinal absorption. The results indicate that cimetidine and antacids should not be given together, and that the dose of cimetidine may have to be increased if it is administered concomitantly with metoclopramide.
    Type of Medium: Electronic Resource
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