BIOTRANSFORMATION AND ELIMINATION OF l-NITROPYRENE IN THE ISOLATED PERFUSED LUNG∶ EFFECTS OF PRETREATING RATS WITH PHENOBARBITONE, β-NAPHTHOFLAVONE, BENZ(A)ANTHRACENE OR THEIR MIXTURES

The isolated perfused rat lung (IPL) was perfused with 60 ml of recirculating Krebs Ringer solution containing 150 μg of l-nitropyrene (l-NP) for 1 h. The l-NP was administered to the IPL by the intratracheal or intravascular route. At specific time points after l-NP administration, perfusate samples were removed from the IPL and analysed for l-NP and its metabolites by HPLC. Monohydroxynitropyrenes , dihydroxynitropyrenes and l-NP were found to be present in the perfusate. The time course of l-NP concentrations in the perfusate could be described by a one compartment pharmacokinetic model. Pretreatment of rats with β-naphthoflavone (BNF), benz(a)anthracene(BA) or a mixture of phenobarbitone (PB) and BNF (PB+BNF) significantly enhanced the metabolism of l-NP and decreased the mean residence time (MRT) of l-NP in the perfusate. Pretreatment of rats with these mixed function oxidase inducers also increased significantly the absorption of l-NP by the lung when it was administered intratracheally. In contrast, pretreatment of rats with PB did not appear to have any effect on the pharmacokinetics of l-NP in the IPL.