The pharmacokinetics of pentane, a by-product of lipid peroxidation

Pentane excretion in breath has been used as an index of lipid peroxidation in intact animals based on the premise that the hydrocarbon is metabolically inert. However, it is now known that pentane is metabolized by animals and that its pulmonary excretion is affected both by its production and by its metabolism. Thus, changes in pentane metabolism could obscure alterations in the rate of production, which is the quantity most closely related to the extent of lipid peroxidation. The purpose of this study was to determine the clearance of pentane from arterial blood by the rat following an injection of the hydrocarbon into a closed chamber containing the animal. Clearance was estimated from the analysis of arterial blood and chamber air concentration-time curves using a three-compartment model which included the chamber as a peripheral compartment. The required blood-to-air partition coefficients were determined experimentally. Blood clearance values obtained from control rats, rats pretreated with carbon tetrachloride, and animals given 4-methylpyrazole were 0.141, 0.021, and 0.014 liter/min/kg, respectively. The 85% decrease in clearance of animals pretreated with either a metabolic inhibitor or a toxin which destroys cytochrome P-450 suggests that metabolism may contribute significantly to the overall elimination of pentane. Therefore, the quantitation of pentane excretion rate as an index of lipid peroxidation should include a consideration of possible changes in metabolic clearance.