Interleukin-2 and blood brain barrier in cats: pharmacokinetics and tolerance following intrathecal and intravenous administration.
Single bolus doses of glycosylated human interleukin-2 (n IL-2) in the range of 2.8 x 10(3) to 2.0 x 10(6) IU/kg were administered to anesthesized cats via the cephalic vein (n = 10) or using suboccipital puncture (n = 8). CSF (cerebrospinal fluid) and blood samples were collected by repeated puncture. The n IL-2 concentration in four cats was determined on the basis of its biologic activity using 3H-thymidine incorporation into human ConA-blasts and by radioimmunoassay. In additional experiments radioactivity was determined in cerebrospinal fluid and serum after intravenous and intrathecal (i.th.) application of 5.8 x 10(3) - 3.2 x 10(3) IU/kg of 14C-acetyl-n IL-2 in regular time intervals. CSF and serum concentration time-profiles show a biexponential decline in the plasma elimination phase with half-lives of 4 min (alpha-phase) and 90 min (beta-phase) after intravenous and 20-120 min (alpha-phase) and 2-16 hours (beta-phase) after intrathecal application. There is a trend towards longer terminal elimination half-lives with increasing doses. Interleukin-2 is able to penetrate the blood brain barrier from the circulation into the cerebrospinal fluid and vice versa. Due to a slow rate of penetration and rapid elimination from blood only traces of n IL-2 (2-8 IU/ml) are detected in CSF after i.v. injection of 2 x 10(6) IU/kg, whereas concentrations between 400 and 1600 IU/ml are maintained in CSF for several hours following i.th. administration of 2-10 x 10(5) IU/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
R
R
Department of Neurology, University of Wurzburg, Germany.
Schwuléra
U
U
Menke
G
G
Rudolph
W
W
Buch
K
K
Fasold
H
H
Lissner
R
R
Thrun
A
A
Krauseneck
P
P
Bogdahn
U
U
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002415:Cats; D004355:Drug Stability; D004361:Drug Tolerance; D005260:Female; D007275:Injections, Intravenous; D007278:Injections, Spinal; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics*; D008297:Male
D007376:Interleukin-2