Pharmacokinetics of interferon in blood, cerebrospinal fluid, and brain after administration of modified polyriboinosinic-polyribocytidylic acid and amphotericin B.

Polyriboinosinic-polyribocytidylic acid (with a sedimentation coefficient of 9S) prepared in a complex with poly-L-lysine and carboxymethylcellulose (poly ICLC) was given intravenously to rabbits in a priming technique with two infusions 4 hr apart; and with low-dose amphotericin B (AmB, 0.5 mg) to trace the transfer of interferon (IFN) in serum to cerebrospinal fluid (CSF) and brain. Peak titers of IFN in serum were at 4 hr, but peak titers of IFN in CSF and brain occurred at 8 hr. At 4 hr, CSF IFN was 0.6%-2.7% of serum titers but at 8 hr had increased to 11.7%-51.1%. IFN was uniformly distributed to all areas of the brain and spinal cord at 8 hr. Titers of IFN in the brain were independent of CSF values, and varied from 5.9%-44.1% of the serum titers. When two injections of poly ICLC were given 4 hr apart, IFN titers in serum, CSF, and brain were significantly raised. Poly ICLC together with AmB increased serum IFN.