TY - JOUR T1 - METABOLISM OF XENOBIOTICS BY THE ISOLATED PERFUSED LUNG JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 433 LP - 442 VL - 2 IS - 5 AU - F. C. P. LAW AU - T. E. ELING AU - J. R. BEND AU - J. R. FOUTS Y1 - 1974/09/01 UR - http://dmd.aspetjournals.org/content/2/5/433.abstract N2 - The metabolism of xenobiotics by an isolated perfused rabbit lung (IPL) preparation was studied, and the metabolites formed were compared to those produced by in vitro lung homogenate and microsomal fractions. Methadone, pentobarbital, and parathion were metabolized to the extent of 10-40% in the IPL, whereas chlorcyclizine and imipramine were apparently not degraded. These xenobiotics were biotransformed by homogenate and microsomal fractions of lung or liver that were fortified with NADPH. In general, the same metabolites were formed from these chemicals by the IPL and subcellular fractions of the lung and liver. Methadone, pentobarbital, and parathion metabolism by the PL was examined in more detail. The major metabolites (exractable by organic solvents) were: for methadone, 1,5-dimethyl-3,3-diphenyl-2-ethylidenepyrrolidine and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline; for pentobarbital, d- and l-diastereoisomers of pentobarbital alcohol; and for parathion, paraoxon. The appearance of metabolite in the perfusate of IPL was also monitored. Methadone and pentobarbital metabolite concentrations increased rapidly after substrate introduction and leveled concentration in 2-4 hr. In contrast, paraoxon concentration in IPL perfusate was found to plateau in 10-20 min. Copyright © 1974 by The American Society for Pharmacology and Experimental Therapeutics ER -