Pharmacokinetics of N-Methyldiethanolamine Following Acute Cutaneous and Intravenous Dosing in the Rat

Abstract

The pharmacokinetics and tissue distribution of N-methyldieth-anolamine (MDEA) were studied in the Fischer 344 rat after a single intravenous (50 or 500 mg/kg) or cutaneous dose (500 mg/kg for 6 or 72 h contact). Topically applied MDEA was well absorbed by both male and female rats (17–21% and 41–50% after 6 and 72 h contact, respectively), after apparently being first sequestered in the skin and later slowly released into the bloodstream. Distribution of MDEA was relatively uniform throughout the major organs, with the highest concentrations being in the liver and kidney. MDEA was substantially metabolized. Metabolism of MDEA could be saturated at high dosages since nonlinear kinetic behavior was observed in rats dosed intravenously with 500 mg/kg. The predominant excretion route for MDEA was in the urine. Urinary excretion of MDEA was slow, with an excretion half-life in excess of 30 h following cutaneous dosing. Metabolites constituted the major fraction in urine, indicating that metabolism plays an important role in MDEA elimination.