Pharmacokinetics of Human Interferon-Beta in Monkeys

Abstract

Human fibroblast-derived interferon (HuIFN-β) was administered to cynomolgus monkeys i.m. (2 × 10⁵ iu/kg), i.v. (2 × 10⁵ iu/kg) or intrathecally (3 × 10⁵ iu/monkey) or given by a 3 hr i.v. infusion (2 × 10⁵ iu/kg). One hr after intrathecal administration, interferon titers in the CSF were 1000–2000 iu/ml, and declined to <10 iu/ml during the first 24 hr. At the same time only minute amounts of HuIFN-β were found in the sera of these animals. After i.m. administration, 5 iu/ml were found on average in the serum during the first 8 hr, with no interferon titer ever exceeding 10 iu/ml. No antiviral activity was found 24 hr after HuIFN-β injection. HuIFN-β injected i.v. resulted in serum interferon titers of approx. 300 iu/ml 30 min after administration, which then decreased to about 5 iu/ml during the first 8 hr 24 hr after injection no antiviral activity was detectable. Daily HuIFN-β i.v. administrations over a period of four days did not affect the interferon clearance from the circulation. During HuIFN-β infusion, constant HuIFN-β titers of about 80 iu/ml were observed which then decreased during the following 5 hr to 2 iu/ml. The choice between a single i.v. injection, resulting in high serum titers for a few minutes, and a 3 hr infusion, resulting in an about fourfold lower but constant interferon level for over two hr, will depend on the mechanism of interferon action in vivo and on the question as to whether side effects can be diminished by infusion.