Urinary and biliary excretion kinetics of 1-hydroxypyrene following intravenous and oral administration of pyrene in rats.
The urinary and biliary excretion kinetics of 1-hydroxypyrene (1-OHP) were compared in male Sprague-Dawley rats exposed intravenously and orally to 1.5, 5, 15, 50 and 100 micromol/kg pyrene. Urine and bile samples were collected at 6-h intervals for up to 24 h. Results showed that the kinetics of 1-OHP were similar for both biliary and urinary excretion whatever the administered dose or exposure route. Furthermore, the time course of 1-OHP excretion in either bile or urine following intravenous dosing resembled that observed after oral administration. In addition, the exposure route and dose had no significant effect on the fraction of dose recovered in urine and bile as 1-OHP after 6, 12, 18 and 24 h post-dosing. Following intravenous injection of 1.5, 5, 15, 50 and 100 micromol/kg pyrene, the mean cumulative percent of dose excreted as 1-OHP in urine over 24 h ranged from 1.7 to 3.2%, while biliary values ranged from 6.5 to 9.5%. Correspondingly, after oral administration, on average, 2.6-3.3% of dose was excreted as 1-OHP in urine and 7.9-10.9% was recovered in bile. Overall, the linear dose-excretion relationship following either exposure routes supports the usefulness of 1-OHP in urine as a bioindicator of polycyclic aromatic hydrocarbon (PAH) exposure. Results further suggest that tissue uptake and distribution of intravenously and orally administered pyrene proceeds similarly. By comparing these data with predicted values from a previously published physiologically based pharmacokinetic model for pyrene in the rat, it also appears that a small fraction of pyrene dose (12%) remains in the body after 24 h and that metabolites other than 1-OHP as measured in the current study are present in significant proportions in urine and feces.
Département de médecine du travail et d'hygiène du milieu, Faculté de médecine, Université de Montréal, Québec, Canada.
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D000284:Administration, Oral; D000818:Animals; D001646:Bile / Q000737:chemistry / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D007275:Injections, Intravenous; D008297:Male; D009153:Mutagens / Q000493:pharmacokinetics*; D011721:Pyrenes / Q000008:administration & dosage / Q000032:analysis / Q000378:metabolism* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014556:Urine / Q000737:chemistry
D009153:Mutagens; D011721:Pyrenes; C030984:pyrene; C033146:1-hydroxypyrene