Summary
Six maturity onset diabetic patients took glibenclamide 5 mg by mouth, every morning 10 min before a standard breakfast. Serum levels of immunoreactive glibenclamide, glucose and immunoreactive insulin were measured repeatedly on the first and 15th days of treatment. Measured glibenclamide blood levels were in close agreement with an analogue computer simulation of data obtained from healthy volunteers: there was no accumulation of drug in the blood, but there was strong evidence for the existence of a slowly equilibrating “deep” compartment. Considerable insulin release and correction of the breakfast-induced hyperglycaemia were observed immediately after administration of the drug, as well as 5 h later, at lunch time. The clinical significance of blood levels of glibenclamide, as well as the correlation of pharmacokinetics with pharmacodynamics, are discussed in the light of these results.
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Abbreviations
- IR-:
-
immuno-reactive
- GLI:
-
glibenclamide
- IRI:
-
immuno-reactive insulin
- GLU:
-
glucose
- AK 1:
-
values obtained with patient AK on the first day of treatment
- AK 15:
-
values obtained with patient AK on the 15th day of treatment
- b:
-
serum level
- bmax :
-
maximal serum level
- t:
-
time after dose
- tmax :
-
time of maximal serum level
- G:
-
gastro-intestinal system
- B:
-
central compartment (blood)
- T:
-
peripheral compartment (tissue)
- E:
-
excreta
- M,N:
-
coefficients of the equation of a bi-exponential decay curve
- µ, v:
-
exponents of the equation of a bi-exponential decay curve
- e:
-
base of natural logarithms
- KBG KEB KTB KBT :
-
first order rate constants (e. g. KBG means: into B, from G)
- K“BG” :
-
first order rate constants
- etc.:
-
not corrected for the volume of distribution
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Zahnd, G. R., Balant, L.: In preparation
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Balant, L., Zahnd, G.R., Weber, F. et al. Behaviour of glibenclamide on repeated administration to diabetic patients. Eur J Clin Pharmacol 11, 19–25 (1977). https://doi.org/10.1007/BF00561783
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DOI: https://doi.org/10.1007/BF00561783