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 To this end, murine NGF was administered to adult rats and multiple blood samples were withdrawn at intervals.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 (t1/2 about 1.5 h) followed by a slow elimination phase (t1/2 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.