Effects of cigarette smoke and 3-methylcholanthrene on the disposition of phencyclidine and its N-ethylamine analogue in the isolated perfused lung of rats.
The isolated perfused lung (IPL) of rats were used to examine the pulmonary disposition and metabolism of radiolabeled phencyclidine (PCP) and N-ethyl-1-phenylcyclohexylamine (PCE). The IPL removed PCP and PCE from the perfusate and converted them to free and conjugated metabolites. At the conclusion of a 1-h perfusion, the lung accumulated at least 20% of the administered radioactivity and metabolized more than 30% of the added drug. Pretreatment of rats with 3-MC or cigarette smoke enhanced significantly PCP and PCE metabolism by the IPL. The concentration of conjugated PCE metabolite in the perfusate of the IPL was increased significantly by both 3-MC and cigarette smoke pretreatments whereas the concentration of conjugated PCP metabolite was not affected by cigarette smoke exposure and increased only slightly after 3-MC pretreatment. Pretreatment of rats with 3-MC or cigarette smoke also altered the amount of radioactivity accumulated by the lung tissue at the conclusion of a 1-h perfusion. Inasmuch as PCP and PCE are often abused by humans via smoke inhalation, a significant amount of these drugs may be stored or metabolized by the lung.
D000818:Animals; D001273:Atmosphere Exposure Chambers; D003514:Cyclohexylamines / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D010622:Phencyclidine / Q000378:metabolism*; D010947:Plants, Toxic; D051381:Rats; D011919:Rats, Inbred Strains; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana; D014316:Tritium
D003514:Cyclohexylamines; D012906:Smoke; D014316:Tritium; D008748:Methylcholanthrene; D010622:Phencyclidine; C023851:N-ethyl-1-phenylcyclohexylamine