POSSIBLE OCCURRENCE OF DRUG INTERACTION BETWEEN FLUOXETINE AND GLIMEPIRIDE IN TWO DISSIMILAR SPECIES

ABSTRACT

The aim of the study is to investigate the effects of fluoxetine pretreatment for 7 days on the hypoglycemic/antidiabetic activity of glimepiride in rats (normal and diabetic) and rabbits. Normal rats, alloxan induced diabetic rats, and normal rabbits of either sex, randomly distributed into   required groups. Fluoxetine per se was carried out in the first part of the investigation. The hypoglycemic/antidiabetic activity was carried out in the next part of the investigation and then in the final phase, fluoxetine was administered for 7 consecutive days and on 8^th day, one hour after the administration of fluoxetine, glimepiride was administered. Blood samples were collected from retro orbital sinus of rats and from marginal ear vein of rabbits at different intervals up to 24h and were analyzed for blood glucose concentrations by GOD/POD method. Onset, peak and duration of hypoglycemia were used as parameters of the investigation. Fluoxetine per se did not alter the blood glucose levels in both rats and rabbits. However, pretreatment with fluoxetine potentiated the peak and duration of hypoglycemia induced by glimepiride in normal/diabetic rats and rabbits. Hence, it is inferred that there is every possibility of occurrence of drug interactions during concomitant usage of therapeutic doses of fluoxetine and glimepiride. Therefore, therapeutic monitoring may be required to avoid the possibility of complications of severe hypoglycemia.

Key words: Fluoxetine, Glimepiride, Alloxan, Antidiabetic activity.