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  • 1
    ISSN: 1432-1440
    Keywords: Type II diabetics ; Treatment of late failure with oral drugs ; Insulin ; Glibenclamide ; Combination treatment ; C-Peptide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a double-blind placebo-controlled cross-over study eight type II diabetics (three men, five women), of whom six were at the point of late failure to oral treatment, were given an insulin infusion of 22 U human insulin/patient for 45 min (∼7 mU/kg × min); 30 min before infusion either glibenclamide (1 tablet Euglucon N) or placebo was administered. Glucose in venous blood, C-peptide, insulin, and glibenclamide concentrations in the blood plasma were simultaneously determined over a period of 210 min. The monitoring of glucose was handled using a Biostator. The insulin level reached a mean maximum of 400 to 500 µU/ml and was in a behavior of 100 µU/ml for 60 min. The areas under the concentration-time curves (AUCs) were practically identical in the two regimes. The blood glucose fell (in mean) from 260 mg/dl to 135 mg/dl and at the end of the experiment was in the range of 155 mg/dl. The glibenclamide concentrations reached maximal concentrations of 185 ng/ml 90 min after administration. The C-peptide concentrations fell in the placebo phase by more than 40%. In contrast, in the glibenclamide period there was at first a slight rise and later a slight marginal fall (initial, 2.0 ng/ml vs 1.9 ng/ml; 60 min, 1.3 ng/ml vs 1.8 ng/ml; 180 min, 1.2 ng/ml vs 1.8 ng/ml). Values after 90, 120, and 180 min were statistically different. The AUCs (0–180 min) were different (329 ng × min/ml vs 251 ng × min/ml). The inhibition of insulin secretion (measured by C-peptide) caused by exogenous insulin administration is largely abolished by glibenclamide. This mechanism could be a major cause for the reduction of the insulin requirement in type II diabetics that has been shown in numerous clinical studies during simultaneous treatment with glibenclamide.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 4 (1971), S. 32-37 
    ISSN: 1432-1041
    Keywords: Glibenclamide ; pharmacokinetics ; metabolism ; potentiation of hypoglycemic action ; phenylbutazone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Description / Table of Contents: Summary Metabolically healthy subjects were given an intravenous injection of 1,13 mg14C-labelled glibenclamide (HB 419). The plasma level, renal elimination of the radioactivity and metabolism of the substance were investigated. Two minutes after administration the HB 419 is virtually present only in the blood and at the end of the distribution period mostly in the extracellular space. 53% of the radioactivity is excreted via the kidneys in the form of metabolites. If glibenclamide is administrated in the same way to the same subjects after pretreatment with phenylbutazone there are no differences in the course of the plasma levels or the rate of elimination from the blood. There is, however, a significant difference in the excretion of the radioactivity in the urine. In the presence of phenylbutazone significantly less HB 419 metabolite is excreted renally. In view of the known alternative route of elimination it is suggested that the amount not excreted in the urine is in compensation eliminated via the bile. There was no difference in the metabolism of glibenclamide between the control and phenylbutazone treated groups. The potentiation by phenylbutazone of HB 419 action, and probably also that of other antidiabetic sulphonylureas, must therefore be due predominantly to other causes (Communication III).
    Notes: Zusammenfassung Stoffwechselgesunde Versuchspersonen erhielten14C-markiertes Glibenclamid in einer Dosis von 1.13 mg/Vpn i.v. gespritzt. Plasmaspiegelverläufe, renale Elimination der Radioaktivität und die Metabolisierung der Substanz wurden untersucht. Zwei Minuten nach der Applikation ist HB 419 praktisch nur im Blutund nach Abschluß der Verteilung weitgehend im Extracellulärraum vorhanden. 53% der Radioaktivität werden über die Nieren in Form von Metaboliten ausgeschieden. Wird den gleichen Probanden nach Prämedikation mit Phenylbutazon Glibenclamid in gleicher Weise verabfolgt, ergibt sich kein Unterschied hinsichtlich der Plasmaspiegelverläufe und der Eliminationsgeschwindigkeit aus dem Blut. Ein signifikanter Unterschied besteht jedoch in der Ausscheidung der Radioaktivität in den Harn (26.3%). In Gegenwart von Phenylbutazon wird ein signifikant geringerer Anteil von HB 419-Metaboliten renal eliminiert. Aufgrund des bekannten zweiten Ausscheidungsweges wird vermutet, daß der fehlende Anteil kompensatorisch über die Galle eliminiert wird. Die Metabolisierung von Glibenclamid weist keine Differenzen zwischen Phenylbutazon-und Kontroll-Gruppe auf. Die Wirkungspotenzierung von HB 419 — wahrscheinlich auch diejenige anderer antidiabetisch wirksamer Sulfonylharnstoffe — durch Phenylbutazon dürfte demnach überweigend andere Ursachen haben. (Mitteilung III).
    Type of Medium: Electronic Resource
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