Uptake and metabolism of [3H]-Leu-enkephalin following either its intraperitoneal or subcutaneous administration to mice.

The uptake and metabolism of 30 micrograms/kg [3H]-Leu-enkephalin ([3H]-LE) following either intraperitoneal (IP) or subcutaneous (SC) administration to Swiss Webster mice was examined. Uptake of [3H] was rapid, with peak levels of radioactivity in plasma observed at 5 or 10 min following IP or SC peptide injection, respectively. The majority (80-99% +/- 0.8) of plasma radioactivity at all postinjection plasma collection time points was in the form of tyrosine-containing enkephalin metabolites, indicating a substantial and rapid in vivo hydrolysis rate for exogenously administered LE. Leu-enkephalin is metabolized in vivo faster than previously reported in vitro in mouse plasma. However, despite this extensive hydrolysis, levels of intact LE remaining in plasma following its systemic administration are within or above endogenous LE plasma levels.