健常人でみたインターフェロン‐β急速静注時の薬物動態および安全性 点滴静注との対比

Abstract

Human beta interferon (HuIFN-β) is a natural glycoprotein with antiviral, antiproliferative, and immunomodulatory properties. The administration of HuIFN-β by intravenous (iv) infusion has been shown to have an antiviral effect on HBe antigen-positive chronicactive hepatitis.In order to evaluate the pharmacokinetics and biological effects of iv bolus administrationof HuIFN-βas compared with iv infusion, we studied ten healthy male volunteers whoreceived a single injection of 3×106IU of HuIFN-βby either bolus administration over5 min or infusion over 1hr.The pharmacokinetic study showed that high peak serum IFN levels were achieved at5min but HuIFN-β was cleared rapidly in the five volunteers receiving HuIFN-βbybolus. On the other hand, constant low levels of circulating HuIFN-βby infusion wereseen in the other five volunteers.The interferon-induced intracellular enzyme 2', 5'-oligoadenylate synthetase (2-5 AS), which is known to be one of the mediators of the antiviral activity of IFN and is suggested to be a convenient marker for interferon therapy, was also measured in serum.Both iv bolus and infusion administration resulted in significant elevation of 2-5 ASactivity which remained stable from 24 hr to 72 hr after the injection, while IFN was nolonger detectable in serum.The rate of induction of the 2-5 AS activity was equivalent following each method ofadministation despite the different IFN pharmacokinetic profiles. There were no significant changes in laboratory findings and side effects by iv bolus or infusion administrationof HuIFN-β.These results may substantiate the usefulness of iv bolus administration of HuIFN-βtopatlents.