1982 Volume 25 Issue 3 Pages 213-220
The plasma concentration of glibenclamide as used in routine clinical practice was measured by a previously reported radioimmunoassay. The glibenclamide concentration in fasting morning plasma of diabetic patients undergoing treatment with the drug for more than one month was variable and often undetectable (<5ng/ml) but roughly paralleled the dosis. The mean levels were 8.5, 12.5 and 17.2 ng/ml in patients taking 2.5 mg and 5 mg as a single dose and 5 mg as two divided doses, respectively. After a single oral administration of 2.5 mg and 5 mg in glibenclamide-treated patients, the drug level in the plasma reached peaks of 82±27ng/ml and 149 ±60 ng/ml at 90 and 120 min, respectively, and declined thereafter with half-lives of 2.7 and 2.9 hr. In normal subjects who were given a single dose of 2.5 mg orally, the peak concentration was 72±32 ng/ml and the half-life was 2.3 hr. In diabetic patients with chronic renal failure and with liver cirrhosis, the peak concentrations of the drug after an oral dose of 2.5 mg were 59±20 and 86±43ng/ml, and the half-lives were 2.8 and 3.5 hr, respectively. The half-life of the drug in patients with liver cirrhosis was prolonged. Comparison between a single dose and two divided dose schedules of 5 mg glibenclamide, revealed that the profiles of the blood glucose and plasma insulin did not differ significantly at most times of the day, although the profiles of the drug level differed between different dose schedules increasing each time after administration. The plasma of patients who were taking tolbutamide, acetohexamide and chlorpropamide interfered significantly with the binding of 3H-glibenclamide to the antiserum. This cross-reaction might be potentially useful as a means of detecting various sulfonylurea drugs in the blood, especially in such cases as factitious hypoglycemia by these drugs.
