Plasma and cerebrospinal fluid pharmacokinetics of recombinant interferon alpha A in monkeys: comparison of intravenous, intramuscular, and intraventricular delivery.
Interferons are currently undergoing clinical testing in patients with cancer and other diseases. A variety of routes of administration 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.
D000818:Animals; D007273:Injections, Intramuscular; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D007370:Interferon Type I / Q000008:administration & dosage / Q000378:metabolism*; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D008433:Mathematics; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution
D007370:Interferon Type I; D011994:Recombinant Proteins