PT  - JOURNAL ARTICLE
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
TI  - Deuterium isotope effect on the toxicokinetics of monomethylamine in the rat.
DP  - 1990 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 447--452
VI  - 18
IP  - 4
4099  - http://dmd.aspetjournals.org/content/18/4/447.short
4100  - http://dmd.aspetjournals.org/content/18/4/447.full
SO  - Drug Metab Dispos1990 Jul 01; 18
AB  - 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.