Effect of Different Bile Salts on the Relative Hypoglycemia of Witepsol W35 Suppositories Containing Insulin in Diabetic Beagle Dogs.

Insulin suppositories were formulated using Witepsol W35 as a base to investigate the effect of various bile salts/acids on the plasma glucose concentration of diabetic beagle dogs. Comparison of the effect of these formulations was made with that produced by insulin subcutaneous injections. Of the bile salts/acids studied, incorporation of l00mg off deoxycholic acid (DCA), sodium cholate (NaC), or sodium deoxycholate (NaDC) with insulin (10 U/Kg) showed that suppositories containing NaDC produced the highest area under the curve (A UC) and relative hypoglycemia (RH) off 290 ± 83 mg%h and 28% ± 8.1%, respectively. To study the optimum amount of NaDC in insulin suppositories to produce the highest RH, 50-200mg/suppository were used, and we found that 150mg NaDC produced 35% ± 13% RH. We also studied the influence of different doses of insulin (5-20 U/kg) in the presence of NaDC ( l00mg). It was found that increase of the insulin dose was accompanied by an increase in AUC and maximum reduction in plasma glucose level C[SUBmax]. A combination of NaDC (100 mg) and NaC (50 mg) produced an AUC of 252 &lusmn; 13 mg%h and an RH of. [ABSTRACT FROM AUTHOR]

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