Plasma levels following intranasal and intravenous administration of human interferon-beta to rabbits.
Rabbits were given single doses (2 x 10(6) IU) of human fibroblast interferon (HuIFN-beta) by the following routes of administration: (a) intravenous injection, (b) dropwise intranasal administration of a liquid dosage form, and (c) spraywise intranasal administration of a powder dosage form. Following the intravenous injection, plasma HuIFN-beta concentrations declined rapidly in a biphasic manner in agreement with a two-compartment model, whilst concentrations following the intranasal administrations conformed to a one-compartment model. Maximum plasma levels and the areas under the plasma concentration-time curve (AUC) in response to dose were studied in the case of the spray administration, and found to be proportional to dose. The systemic bioavailability of HuIFN-beta (administered with sodium glycocholate and excipients) via the nasal routes was about 3% of that via the intravenous route. The elimination half-lives did not differ significantly between these two routes of administration.
Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Y
Y
Maitani
T
T
Igawa
Y
Y
Machida
T
T
Nagai
D000281:Administration, Intranasal; D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005079:Excipients / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D007370:Interferon Type I / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D011208:Powders; D011817:Rabbits; D012996:Solutions
D001647:Bile Acids and Salts; D005079:Excipients; D007370:Interferon Type I; D011208:Powders; D012996:Solutions