Abstract
The pharmacokinetics of IFN after subcutaneous (s. c.) administration of IFN-minipellet, a new sustained release formulation of IFN, were investigated in rabbits. The serum IFN level was elevated slowly and reached the maximal level 7 hours after the administration of IFN-minipellet, while s.c. administration of aqueous solution presented a rapid elevation of IFN level in sera, The serum IFN concentration decreased gradually thereafter. No sharp peak suggesting an initial burst was seen. IFN was still detectable in sera 7 days after the administration. Serum IFN levels after the administration of IFN-minipellets in different lengths (i. e. different doses) were proportionally dose-dependent, and it was indicated that the release property of IFN from IFN-minipellet was not affected by the length of minipellet. S. c. administration of IFN-minipellet in abdominal, femoral, and dorsal region provided similar time courses of IFN concentration in sera. These results showed that the release of IFN from IFN-minipellet in vivo was wellcontrolled and continued over 7 days. The local toxicity of subcutaneously administered IFN-minipellet in rabbits was slso investigated by observing the administration site for 1 week. No inflammatory reaction around IFN-minipellet was seen. IFN-minipellet was considered to be highly biocompatible. Clinical investigations revealed that IFN minipellet caused much less side effects than conventional IFN therapy while their therapeutic effects were comparable. The mechanism of this phenomenon was discussed from the viewpoint of pharmacokinetics. It was suggested that the slow release of IFN may be the key to the low pyrogenicity of IFN-minipellet. IFN-minipellet seems to be highly useful in the treatment of clonic hepatitis C to improve QOL of patients by reducing the frequency of administration and adverse effects.
