Biotransformation and elimination of 1-nitropyrene in the isolated perfused lung: effects of pretreating rats with phenobarbitone, beta-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 micrograms of 1-nitropyrene (1-NP) for 1 h. The 1-NP was administered to the IPL by the intratracheal or intravascular route. At specific time points after 1-NP administration, perfusate samples were removed from the IPL and analysed for 1-NP and its metabolites by HPLC. Monohydroxynitropyrenes, dihydroxynitropyrenes and 1-NP were found to be present in the perfusate. The time course of 1-NP concentrations in the perfusate could be described by a one-compartment pharmacokinetic model. Pretreatment of rats with beta-naphthoflavone (BNF), benz(a) anthracene (BA) or a mixture of phenobarbitone (PB) and BNF (PB + BNF) significantly enhanced the metabolism of 1-NP and decreased the mean residence time (MRT) of 1-NP in the perfusate. Pretreatment of rats with these mixed-function oxidase inducers also increased significantly the absorption of 1-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 1-NP in the IPL.