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Kinetics of tissue distribution and elimination of pyrene and 1-hydroxypyrene following intravenous administration of [14C]pyrene in rats.

The tissue distribution and elimination of pyrene and 1-hydroxypyrene (1-OHP) were evaluated in male Sprague-Dawley rats (210-240 g) following an intravenous injection of 50 micromol/kg of [14C]pyrene. Blood and tissues were removed and urine and feces were collected at 1, 2, 4, 8, 16, and 24 h postdosing. [14C]Pyrene equivalents were measured by liquid scintillation counting, and beta-glucuronidase/arylsulfatase-treated blood, tissues, and excreta were analyzed for pyrene and 1-OHP by HPLC/fluorescence. At 1 h, the largest fraction of the dose was found in adipose tissue, essentially as pyrene, and its elimination followed first-order monophasic kinetics with a half-life (t(1/2)) of 4.9 h. In blood, liver, kidney, lung, muscle, and gastrointestinal (GI) tract, kinetics of [14C]pyrene equivalents were biphasic and average t(1/2) values for the terminal elimination phase (8 to 24 h) ranged between 6.2 and 8.7 h. Elimination of pyrene in blood and these tissues except the GI tract followed first-order biphasic kinetics with average t(1/2) values of the terminal phase ranging between 3.6 and 5.4 h. In the GI tract, a monophasic elimination kinetics of pyrene was observed with mean t(1/2) value of 3.1 h. Kinetics of 1-OHP in blood and liver showed a monophasic elimination with mean t(1/2) values of 6.7 and 6.2 h, respectively. Kinetics of 1-OHP in the other tissues were biphasic with average t(1/2) values of the terminal elimination phase ranging between 5.2 and 6.2 h. At 24 h, on average, 81.7% of the dose was recovered in the urine (57.2%), feces (18.3%), and GI tract (6.2%) as [14C]pyrene equivalents with 2.7 and 1.9% of dose excreted as total 1-OHP in urine and feces, respectively. At all time points, 1-OHP in urine represented a constant fraction of total 14C in urine and feces. These results indicate that (i) [14C]pyrene was rapidly distributed, metabolized, and eliminated from the body, and (ii) although 1-OHP represents a small percentage of total pyrene eliminated from the body, it remains a reliable indicator of systemic exposure to, and overall elimination of the 14C associated with, this polycyclic aromatic hydrocarbon.