ADMINISTRATION ROUTE DEPENDENT BIOAVAILABILITY OF INTERFERON-ALPHA AND EFFECT OF BILE-SALTS ON THE NASAL ABSORPTION

Administration route dependent bioavailability of recombinant human interferon alpha (IFN-alpha) and effect of seven bile salts and polyoxyethylene-9-lauryl ether (BL-9) on nasal absorption of IFN-alpha were studied in rats. IFN-alpha (1.5 x 10(7) IU/kg) was administered through iv, pv, po and ip routes and AUC of the routes were compared. As a result, it was found that IFN-alpha is extracted almost completely during its passage through the GI lumen, and is not absorbed from the GI lumen. Moreover, IFN-alpha sparingly transported through the GI lumen suffers additional extraction by the GI mucosa (57 %) and the liver (8 %) consecutively and only about 40 % of it can reach the systemic circulation. Therefore, a high bioavailability of IFN-alpha cannot be expected through the oral route even with the aid of absorption enhancers. On the other hand, significant absorption of IFN-alpha could be attained through the nasal route with some absorption enhancers (1 % w/v). Among the enhancers examined, sodium cholate (CH), sodium glycocholate (GC), sodium taurocholate (TC), sodium glycodeoxycholate (GDC), sodium taurodeoxycholate (TDC) and BL-9 increased the nasal bioavailability of IFN-alpha. However, sodium dehydrocholate (DHC) and sodium deoxycholate (DOC) did not show such effect. Nasal bioavailability of IFN-alpha was increased up to 32.3 (+/- 15.5) % by 1 % TC. The enhancing effect of TC was significantly (p<0.05) greater than those of CH, DOC, DHC and BL-9. TC and GC seemed to be potential candidates for the nasal absorption enhancers of IFN-alpha, considering that they are reportedly less toxic than GDC and TDC.