PHARMACOKINETICS OF NERVE GROWTH-FACTOR (NGF) FOLLOWING DIFFERENT ROUTES OF ADMINISTRATION TO ADULT-RATS

The suggested potential for therapeutic use of nerve growth factor (NGF) in the treatment of toxic and degenerative disorders of the nervous system indicates a need to determine its pharmacokinetics. To this end, murine NGF was administered to adult rats and multiple blood samples were withdrawn at intervals. NGF levels, determined in plasma samples by a two-site enzyme immunoassay, were used to determine the pharmacokinetics of NGF. These studies demonstrate that murine NGF has a distribution half-life of about 5.4 min and an elimination half-life of 2.3 h following intravenous injection. When administered by subcutaneous (sc) injection, the elimination half-life is prolonged to 4.5 h. Administration of NGF by sc continuous infusion, using mini-osmotic pumps, provides stable, dose-related levels of circulating NGF within few days from pump implantation, Upon removal of the pump, NGF levels show a rapid decay (t(1/2) about 1.5 h) followed by a slow elimination phase (t(1/2) about 150 h). These pharmacokinetic parameters might serve for selection of an appropriate administration route and dose regimen that would optimize schedule-dependent expression of NGF therapeutic activity. (C) 1994 Academic Press, Inc.