TY - JOUR T1 - Deuterium isotope effect on the toxicokinetics of monomethylamine in the rat. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 447 LP - 452 VL - 18 IS - 4 AU - A J Streeter AU - R W Nims AU - P R Sheffels AU - J A Hrabie AU - L Ohannesian AU - Y H Heur AU - B A Mico AU - L K Keefer Y1 - 1990/07/01 UR - http://dmd.aspetjournals.org/content/18/4/447.abstract N2 - The single-dose toxicokinetics of monomethylamine has been characterized in the rat by HPLC assay of serial blood samples. Biphasic first-order elimination was observed following an iv bolus dose of 19 mumol/kg with a terminal half-life of 19.1 +/- 1.3 min (mean +/- SE, N = 4). The apparent steady state volume of distribution, systemic blood clearance, and renal blood clearance were 1.21 +/- 0.09 liter/kg, 53.4 +/- 3.5 ml/min/kg, and 5.72 +/- 0.53 ml/min/kg, respectively. The administration of an intragastric dose permitted the calculation of the systemic bioavailability of monomethylamine as 69 +/- 3%. Duplicate experiments using the structural analogue with deuterium atoms substituted for hydrogens on the methyl group revealed a much slower elimination of the compound, although ultimately, 5 times as much was excreted unchanged in the urine. Isotope effects calculated as the ratios of terminal half-life, systemic blood clearance, and systemic bioavailability were 1.9, 2.2, and 1.8, respectively. ER -