Najma Sultana, Saeed Arayne, Noman Ahmed.
In vitro availability of Metformin in presence of H2 receptor antagonists.
Pak J Pharm Sci Jan ;19(1):28-33.

Metformin is a guanidine derivative used for the treatment of NIDDM. As it is used for a long-term therapy, it may be coadministered with other drugs. Present paper deals with the in vitro availability studies of metformin in presence of commonly used H2 receptor antagonists. The later drugs compete with histamine for H2 receptors and block gastric acid secretion and some cardiovascular effects of histamine. These studies were carried out in simulated gastric juices, simulating empty and full stomach, simulated intestinal juice and buffers of pH 7.4 simulating blood pH at 37°C on a B.P. 2003 dissolution test apparatus. Commonly prescribed H2 receptor antagonists like cimetidine, ranitidine and famotidine were used in these studies. The present study clearly indicated that availability of metformin can be altered in presence of most of the H2 receptor antagonists studied except in presence of famotidine at pH 4 where the drug concentration remains unaltered. The availability of metformin was increased in simulated gastric juice, pH 7.4 and pH 9 (except ranitidine at pH 9) whereas the decrease in availability was observed in presence of cimetidine and ranitidine at pH 4 and ranitidine at pH 9. On the basis of these results, it is can be suggested that metformin should be coadministered with care along with H2 receptor antagonists especially in case of ranitidine; although chances of adverse reactions are rare but decrease availability of metformin may result in delayed effect. On the other hand, increase in metformin concentration may result in hypoglycemic effects.

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