Plasma and cerebrospinal fluid pharmacokinetics of recombinant interferon alpha A in monkeys: comparison of intravenous, intramuscular, and intraventricular delivery

• Published in: Cancer drug delivery Vol. 2; no. 4; p. 247
• Main Authors: Collins, J M, Riccardi, R, Trown, P, O'Neill, D, Poplack, D G
• Format: Journal Article
• Language: English
• Published: United States 1985
• Subjects: Animals; Injections, Intramuscular; Injections, Intravenous; Injections, Intraventricular; Interferon Type I - administration & dosage; Interferon Type I - metabolism; Kinetics; Macaca mulatta; Male; Mathematics; Recombinant Proteins - administration & dosage; Recombinant Proteins - metabolism; Time Factors; Tissue Distribution
• ISSN: 0732-9482
• DOI: 10.1089/cdd.1985.2.247

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.