engleski

BENZOIC ACID DERIVATIVE HYPOGLYCEMIC ACTIVITY AND PHARMACOKINETICS IN NON-INSULIN-DEPENDENT DIABETIC PATIENTS

The hypoglycemic activity of single dose benzoic acid derivative (AG-EE 388, 3.0 mg) was compared to glibenclamide 3.5 mg open, and to placebo double blind, in 12 non-insulin dependent diabetics in a three-time cross-over trial. The pharmacokinetic features of AG-EE 388 were determined during a 24-hour period. The mean maximal glucose level after AG-EE 388 was 12.5± 4.0 mM/l in the morning, 10.1± 3.0 mM/l in the afternoon and 12.5± 4.0 mM/l during the night. Glucose levels were not significantly different after the administration of glibenclamide (12.7± 3.1, 9.8± 2.9 and 11.9± 3.7 mM/l, respectively). Accordingly, both were significantly lower during the morning and afternoon than after placebo (14.4± 3.2, 12.2± 4.1 and 13.2± 3.6 mM/l, respectively) (Table 1). The mean value of serum insulin concentration after AG-EE 388 in the morning (57.8± 33.6 mU/l) corresponded to the value obtained after glibenclamide (59.7± 28.9 mU/l) and was significantly higher than after placebo (47.3± 31.0 mU/l). In the afternoon, serum insulin concentration remained elevated after glibenclamide (36.0± 14.6 mU/l), and decreased significantly after AG-EE 388 and placebo (29.1± 11.6 and 27.5± 10.7 mU/l, respectively). During the night, there were no significant difference in serum insulin concentration among the three treatments (27.9± 11.8, 25.1 ± 8.5 and 29.9± 12.8 mU/l, respectively). The maximal plasma concentration of 118± 42 ng/ml was achieved 1.4± 1.2 h after the administration of a single oral dose of 3.0 mg AG-EE 388. Terminal biologic half-time = 2.5± 1.4 h. Conclusion: As a potential oral antidiabetic, AG-EE 388 showed promising pharmacokinetic characteristics: fast resorption and short biologic half-time, with a significantly shorter betacyto- tropic activity compared to glibenclamide and insignificant difference in hypoglycemic activity.

benzoic acid derivative; pharmacokinetics; diabetes mellitus; oral therapy

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