HYPOGLYCAEMIC EFFECT OF PULMONARILY DELIVERED INSULIN IN NORMAL RATS

AIM: To investigate the hypoglycaemic effect of pulmonarydelivered insulin solution (INSSOL) on normal rats. METHODS: INSSOL was administered to the exposed trachea of anesthetized normal rats. Blood samples were collected at specified intervals and blood glucose levels were determined by glucose oxidase method. The hypoglycaemic response was examined after intrapulmonary delivery of INSSOL in three doses (0.5, 1.0 and 5.0 u·kg^-1) and under two pH conditions (pH 3 and pH 7), as well as coadministration of protease inhibitor (bacitracin) or absorption enhancers. The pharmacological bioavailability (PBA), calculated from area above the curve (AAC) was used to evaluate the absorption enhancement of INSSOL from the lung under various conditions. RESULTS: In the absence of additives, a low dose of insulin solution (0.5u·kg^-1) produced significant hypoglycaemic effect following intrapulmonary administration, which showed a PBA of 26.0%. The concomitant administration of sodium caprilate, sodium cholate, Brij35, Brij78 as well as bacitracin appeared to be more effective for enhancing the pulmonary absorption of insulin than the other adjuvants like oleic acid, EDTA and 2hydroxypropylβcyclodextrin. Absorption of INSSOL under pH 3 condition was significantly increased compared with that under pH 7 condition. CONCLUSION: Pulmonary delivery of INSSOL produced significant hypoglycaemic effect on normal rats, the pulmonary route may be useful for the delivery of insulin.