Pharmacokinetics and pharmacodynamics of interferon beta-1a (IFN beta-1a) in healthy volunteers after intravenous, subcutaneous or intramuscular administration

The objective of this study was to define the single-dose pharmacokinetics and pharmacodynamics of interferon beta-1a (IFN beta-1a) after various routes of administration. Three groups, each consisting of 8 healthy male and female subjects, received a single 60 mu g (12 million units) dose of IFN beta-1a by either a 30-minute intravenous infusion, or by subcutaneous or intramuscular injection. Serum interferon activity levels peaked immediately after the end of the intravenous infusion and thereafter fit a bioexponential decay model. The mean distribution and elimination half-lives were 4 minutes and 4 hours, respectively. The mean volume of distribution of the central compartment was 61.6L and the mean total clearance was 334 ml/h/kg. Interferon activity was consistently detectable in serum after intramuscular injection but not after subcutaneous injection. After intramuscular injection, peak serum interferon activity levels were approximately 40 U/ml and occurred 12 to 18 hours post-administration. The area under the curve for serum interferon activity was 2- to 3-fold higher after intramuscular injection than after subcutaneous injection. The pharmacodynamic response, as measured by changes in serum neopterin and beta(2)-microglobulin concentrations, was also greatest after intramuscular injection, followed by subcutaneous, then intravenous administration. These results indicate that the optimal pharmacokinetic response is produced by intramuscular, rather than subcutaneous or intravenous, administration of IFN beta-1a.