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INTERACTIVE POTENTIAL OF CLARITHROMYCIN IN RATS ADMINISTERED WITH GLICLAZIDE IN NORMAL AND DIABETIC CONDITIONS

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Author(s): Neelam Raj | Prakash S. B | Vijay Kamat | Shanmukha I | Rajendra SV

Journal: International Research Journal of Pharmacy
ISSN 2230-8407

Volume: 2;
Issue: 9;
Start page: 130;
Date: 2011;
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Keywords: Antidiabetic activity | Clarithromycin | CYP enzymes | Gliclazide.

ABSTRACT
To investigate the interaction between clarithromycin and gliclazide, the present study is designed in various animal models. Albino rats and rabbits were selected for the current study. The animals were suitably grouped. In the first part of the experiment, per se effect with clarithromycin was carried out. In the next phase, the animals were treated with gliclazide and hypoglycemic/antidiabetic activity was performed. In the last phase, the animals of the second part were pretreated with clarithromycin for 7 days and on the 8th day, one hour after clarithromycin administration; the animals were treated with gliclazide. The blood samples were collected from the animals (retro-orbital sinus of rats and marginal ear veins of rabbits) up to 24 h before and after clarithromycin administration and blood glucose levels were analyzed by GOD-POD. Onset, peak effect and duration of hypoglycemia/antidiabetic activity were considered as parameters of the study. Clarithromycin increased the peak effect and duration of hypoglycemia induced by gliclazide in all the animal models. These findings suggested that clarithromycin retarded the metabolism of gliclazide. It was reported that clarithromycin is an inhibitor of CYP 3A4 and further gliclazide is metabolized by CYP 2C9 and CYP 3A4. Hence, increased hypoglycemic/antidiabetic activity may be attributed to clarithromycin induced inhibition of CYP enzyme. Therefore, it may be suggested that during concomitant administration of clarithromycin and gliclazide, the dose and frequency of administration of gliclazide has to be readjusted as a precautionary measure so as to avoid the possibility of hypoglycemia.
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