Effect of cholestyramine on the disposition of pentachlorophenol in rhesus monkeys

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Abstract
Male rhesus monkeys [3] were provided with a bile duct bypass and dosed twice with 14C-pentachlorophenol [an environmental contaminant] (50 mg/kg orally) 4 wk apart. During the 1st day after each dose, the monkeys excreted about 20, 0.5 and 20% of the dose into urine, feces and bile, respectively. While the animals continued to receive basal diet after the 1st dose, starting 24 h after the 2nd dose, their diet was supplemented with 4% cholestyramine for 6 consecutive days. A comparison of control to treatment period (days 2-6) shows that cholestyramine reduced the urinary excretion of pentachlorophenol from 35 to 5% and increased the fecal excretion from 3 to 54% of the dose administered. Cholestyramine, in addition to changing the major route of excretion of pentachlorophenol elimination, also markedly reduced the body burden of pentachlorophenol as total excretion (urinary plus fecal) was enhanced by 40%. Up to 30% of the dose was excreted into bile in 1 day during the control period, indicating considerable enterohepatic circulation of pentachlorophenol. Cholestyramine decreased the amount of pentachlorophenol in the bile from 70 to 52% of the dose, which coincided with a similar decrease in the urine. Apparently a considerable portion of pentachlorophenol in urine originates from the enterohepatic circulation. The increase in the fecal excretion (52% of dose) of pentachlorophenol, as a result of the treatment, exceeded by far the decrease seen in the urine (30% of dose) or bile (18% of dose), suggesting that, in addition to interfering with the enterohepatic cycle of pentachlorophenol, cholestyramine also increases its elimination directly across the intestinal wall.