Serum glibenclamide in diabetic patients, and influence of food on the kinetics and effects of glibenclamide.

The steady state concentrations of glibenclamide in serum were measured radioimmunologically in 37 diabetic patients after administration for at least a year. No other antidiabetic drugs had been given. The interindividual variation in glibenclamide concentrations was extremely large (0 to 1520 nmol/l), greatly exceeding the variation in dosage (2.5--25 mg daily). There was no relation between dose and serum concentration of glibenclamide. Only four (9%) patients had fasting blood glucose concentrations below 5.5 mmol/l, and fewer than half had values below 8 mmol/l. In most cases, therefore, the therapy was inadequate. Single-dose kinetics of glibenclamide was assessed in healthy volunteers. Food intake did not influence the bioavailability of a 5 mg dose of glibenclamide. There was no insulin increase in response to glibenclamide unless a meal was also given, and this increase was not significant until 1 h after administration of drug and meal, when the mean serum concentration of glibenclamide had reached 100 nmol/l. Even in the fasting state, however, there was a progressive fall in blood glucose after glibenclamide administration, significant within 45 min and with a nadir at 2--2 1/2 h.