Plasma and Cerebrospinal Fluid Pharmacokinetics of Recombinant Interferon Alpha A in Monkeys: Comparison of Intravenous, Intramuscular, and Intraventricular Delivery

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Abstract
Interferons are currently undergoing clinical testing in patients with cancer and other diseases. A variety of routes of adminstration are being utilized, and there is particular interest in delivery of interferon to the central nervous system. A biphasic decline in plasma concentrations was observed in monkeys following an i.v. bolus, with initial half-times of 15 to 33 min and terminal half-times of 1.7 to 4.6 hours. Total body clearance ranged from 24 to 39 ml/sq.m/min and steady-state volume of distribution was similar to extracellular space. CSF exposure was 1% or less than that of plasma. Intramuscular injections produced lower peak concentrations and more sustained levels, but there was substantial variation in bioavailability (range 19-103%). Levels in the CSF were not detectable for the i.m. route. For intraventricular doses, CSF exposure was 3,000-fold greater than for i.v. doses, despite a 20-fold lower dose.