The pharmacokinetics of benzo[alpha]pyrene in the isolated perfused rabbit lung: the influence of benzo[alpha]pyrene, n-dodecane, particulate, or sulfur dioxide.
The pharmacokinetics of benzo[a]pyrene (BaP) in the isolated perfused rabbit lung (IPL) following pretreatment of the whole animal or simultaneous administration to the IPL with n-dodecane, ferric oxide, crude airborne particulate (CAP), fly ash or sulfur dioxide have been investigated using a one compartment model. The rate constant for the appearance (ka) of BaP in the blood, the clearance of BaP from the blood, and the rate of appearance of BaP metabolites (RAM) were the kinetic parameters determined. BaP entered the blood rapidly with an average half-life of 11 min in experiments in which the IPLs received only BaP on perfusion. The logarithms of the clearances from these experiments were linearly correlated with the RAMs. In these experiments, pretreatment of the whole animal with BaP produced a 48-55-fold increase in BaP clearance while pretreatment with n-dodecane increased the clearance 4-fold in comparison with no pretreatment. Pretreatment with ferric oxide or ferric oxide and BaP increased the clearance by factors of 5.5 and 1.5, respectively, over those of unpretreated and BaP pretreated experiments.
D000393:Air Pollutants / Q000633:toxicity*; D000473:Alkanes / Q000494:pharmacology*; D000818:Animals; D001564:Benzo(a)pyrene / Q000097:blood / Q000378:metabolism*; D001682:Biological Availability; D004347:Drug Interactions; D005290:Ferric Compounds / Q000494:pharmacology*; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D011817:Rabbits
D000393:Air Pollutants; D000473:Alkanes; D005290:Ferric Compounds; C007548:n-dodecane; C000499:ferric oxide; D001564:Benzo(a)pyrene; D007501:Iron