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Objective: To assess the ability of an anti-lysozyme antibody to stabilize the plasma pharmacokinetics of lysozyme through a ‘buffering’ effect. Methods: Hen egg lysozyme was radiolabeled with 14C and infused with or without the murine anti-lysozyme antibody D1.3 into the jugular vein of rats. The dosages of antibody and lysozyme were varied, and the antibody and lysozyme were administered either together or in separate infusions. Results: Buffering of lysozyme with an equimolar amount of D1.3 more than doubled the plasma half-life of lysozyme and addition of more antibody buffer prolonged the half-life to an even greater extent. D1.3 bound lysozyme that was infused several minutes after the D1.3 administration, indicating that D1.3 can be charged with drug in vivo. Conclusion: Antibody buffering of monovalent therapeutic enzymes is possible and may have potential for clinical use. [ABSTRACT FROM AUTHOR]

Abstract: The efficacy of chemotherapy on brain tumors is often hindered by the presence of the blood brain barrier. This barrier keeps many systemically administered substances from entering the cerebrospinal fluid (CSF), while allowing intrathecally administered drugs free passage out of that compartment. Therefore, achieving a therapeutic concentration of a cell cycle inhibitor in the CSF for a time long enough to have a cytotoxic effect on slow-growing tumor cells has proven difficult. The ability of an antibody to prolong ligand half-life and bioactivity has been previously described occurring in the plasma. This phenomenon has not yet been described or exploited for use in the CSF compartment. Antibodies often have a longer residence time in the CSF than small-molecule drugs, so antibody buffering, administration of a drug with its specific antibody, can prolong the bioactive lifetime of a drug in the CSF. Here we describe antibody buffering of the small molecule hapten 2-phenyl-oxazol-5-one-methylene-γ-amino butyrate in the CSF of a rats. Not only does the presence of an antibody buffer increase the half-life of both total and free hapten in the CSF, but the antibody can be re-charged in situ with fresh hapten, even days after the initial antibody infusion. Antibody buffering may provide a viable option for delivering a stable, bio-available concentration of a drug that is normally rapidly eliminated from the CSF. [Copyright &y& Elsevier]