Sorption of fluoroacetate (compound 1080) by colestipol, activated charcoal and anion-exchange resins in vitro and gastrointestinal decontamination in rats

The sorption of sodium fluoroacetate (FA) by activated charcoal (AC) and 5 anion exchange resins (AERs) was tested in 2 simulated gastrointestinal (GI ) fluids. Each sorbent was incubated with FA in a shaker-water-bath at 37 C for 24 h. Supernatant was removed and filtered, and the concentration of F A was determined by gas chromatographic detection of the dichloroaniline de rivative. Under simulated gastric conditions (0.1 M HCl at similar to pH 1. 5), the sorbents removed the following proportions of FA from solution: Car bosorb(R) AC, 87 +/- 2%; cholestyramine, 28 +/- 7%; colestipol, 96 +/- 0%; Amberlite IRA-96, 70 +/- 2%: DEAE-Sephadex, 7 +/- 4%; Chitosan, 66 +/- 2%. Under simulated intestinal conditions (0.05 M sodium phosphate at similar t o pH 7.4), binding was as follows: Carbosorb(R) AC, 68 +/- 4%; cholestyrami ne, 53 +/- 5%; colestipol, 46 +/- 2%; Amberlite IRA-96, 10 +/- 20%; DEAE-Se phadex, 64 +/- 7%; Chitosan, 5 rt 2%. All findings differed significantly f rom control, with the exception of Amberlite IRA-96 and Chitosan in phospha te buffer, and DEAE-Sephadex in HCl. In a second study, rats were given 5 m g FA/kg, and then gavaged with 2 g/kg Carbosorb(R)AC, colestipol or bentoni te. Over 4 h, the area under the curve of serum FA versus time (AUC) decrea sed by 39% in the rats treated with colestipol and 42% in those treated wit h bentonite. In contrast, Carbosorb(R)AC did not affect the AUG, yet increa sed Tma. In another study, mortality was assessed 96 h after rats were oral ly dosed with 5 mg FA/kg followed by gavage with 2 g/kg Carbosorb(R)AC, col estipol or water immediately or 30 min after dosing. When the sorbents were given immediately, mortality was the same as control (75%). Surprisingly t he 30-min delay resulted in lower mortality in colestipol-treated rats, (si milar to 38%) compared to 100% in the group treated with Carbosorb(R)AC. Be fore any recommendation can be made regarding the use of colestipol as a GI decontaminant, the latter findings require confirmation in an intensive ca re setting. The potential for synergistic effects with 2 or more sorbents a lso warrant investigating.