PHARMACOKINETICS OF RECOMBINANT HUMAN INTERFERON-BETA(SER) IN HEALTHY-VOLUNTEERS AND ITS EFFECT ON SERUM NEOPTERIN

The pharmacokinetics of and biologic response modification by recombinant human interferon-beta(ser) (rIFN-beta(ser)) were evaluated in 12 healthy male volunteers. Subjects received a single intravenous (iv) injection of 90 x 10(6) IU of rIFN-beta(ser) followed by a single or eight consecutive daily 90 x 10(6) IU subcutaneous (sc) doses. Blood samples collected after the iv, first sc, and last sc doses and prior to each sc dose were assayed for interferon antiviral activity and the interferon-inducible marker neopterin. Following iv administration, serum interferon concentrations generally declined biexponentially, with a mean serum clearance of 0.76 +/- 0.28 L/hr-kg, a mean steady-state volume of distribution of 2.88 +/- 1.81 L/kg, and a mean terminal half-life of 4.29 +/- 2.29 hr as determined by noncompartmental analysis. Following sc administration, absorption of rIFN-beta(ser) was prolonged, with serum concentrations generally below 100 IU/mL. No accumulation of rIFN-beta(ser) in serum was noted after eight daily sc injections. In contrast, serum neopterin levels did not increase above baseline levels until 12 hr after iv dosing and 24 hr after sc dosing. The mean increase in serum neopterin at 24 hr post iv injection was significantly greater than that at 24 hr post sc dosing.