In vitro and In vivo drug-drug interaction between Sitagliptin phosphate and Atenolol.

Md. Mosarraf Hossen¥, Mohammad Shah Hafez Kabir¥, Atiqur Rahman, Kazi Ashfak Ahmed Chowdhury*, Mohammed Emranul Huq, Nirjhar Das, Md. Shalah Uddin Pasha, Mohammed Aktar Sayeed, Abul Hasanat

The aim of the present study to evaluate the in vitro and in vivo complexation nature and strength of complex which may be formed due to interaction between sitagliptin phosphate and atenolol. The interaction of sitagliptin phosphate and atenolol has been studied in aqueous system at a fixed temperature (37⁰C) at both gastric pH (pH 1.2 and pH 3.2) and intestinal pH (pH 6.8) by using Job’s method of continuous variation and Ardon’s method. Oral glucose tolerance test (OGTT) was used to identify in vivo DDI in mice. From spectrophotometric study, sitagliptin phosphate and atenolol give different spectra when sitagliptin phosphate mixed with atenolol in 1:1 ratio. The intensity of the spectra of sitagliptin phosphate slightly changes due to interaction. The jobs plot was obtained by plotting absorbance difference against the mole fraction of the each drug at pH 1.2, pH 3.2 and pH 6.8. When the spectra of pure sitagliptin phosphate and atenolol were compared with 1:1, 1:2 and 2:1 mixture, there was a change observed which indicate the formation of 1:1, 1:2 and 2:1 complexes of sitagliptin phosphate with atenolol. The values of stability constant is more than one at al pH (1.2, 3.2 and 6.8), which is the indication of strong complex. The stability constant values are 1.2073, 1.1839 and 1.2075 respectively. From the in vivo observation of Oral glucose tolerance test, at 1:1 complex, blood glucose level decrease (13.88%) less compared to Sitagliptin phosphate (22.22%) significantly. Complex (1:1) showed different activity rather than pure sitagliptin phosphate treatment due to complexation. Therefore, it can be concluded that a careful consideration is needed during concurrent administration of Sitagliptin phosphate with Atenolol.