Sorption of fluoroacetate (compound 1080) by Colestipol, activated charcoal and anion-exchange in 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 FA was determined by gas chromatographic detection of the dichloroaniline derivative. Under simulated gastric conditions (0.1 M HCl at approximately pH 1.5), the sorbents removed the following proportions of FA from solution: Carbosorb 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 approximately pH 7.4), binding was as follows: Carbosorb AC, 68 +/- 4%; cholestyramine, 53 +/- 5%; colestipol, 46 +/- 2%; AmberliteIRA-96, 10 +/- 20%; DEAE-Sephadex, 64 +/- 7%; Chitosan, 5 +/- 2%. All findings differed significantly from control, with the exception of Amberlite IRA-96 and Chitosan in phosphate buffer, and DEAE-Sephadex in HCI. In a second study, rats were given 5 mg FA/kg, and then gavaged with 2 g/kg Carbosorb AC, colestipol or bentonite. Over 4 h, the area under the curve of serum FA versus time (AUC) decreased by 39% in the rats treated with colestipol and 42% in those treated with bentonite. In contrast, Carbosorb AC did not affect the AUC,yet increased Tmax In another study, mortality was assessed 96 h after rats were orally dosed with 5 mg FA/kg followed by gavage with 2 g/kg Carbosorb AC, colestipol or water immediatey or 30 min after dosing. When the sorbents were given immediately, mortality was the same as control (75%). Surprisingiy, the 30-min delay resulted in lower mortality in colestipol-treated rats, (approximately 38%) compared to 100% in the group treated with Carbosorb AC. Before any recommendation can be made regarding the use of colestipol as a GI decontaminant, the latter findings require confirmation in an intensive care setting. The potential for synergistic effects with 2 or more sorbents also warrant investigating.
Norris
W R
WR
National Poisons Centre, University of Otago, New Zealand.
Temple
W A
WA
Eason
C T
CT
Wright
G R
GR
Ataria
J
J
Wickstrom
M L
ML
D000327:Adsorption; D000704:Analysis of Variance; D000818:Animals; D000837:Anion Exchange Resins / Q000627:therapeutic use*; D002606:Charcoal / Q000627:therapeutic use*; D003084:Colestipol / Q000494:pharmacology; D005463:Fluoroacetates / Q000097:blood / Q000633:toxicity*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar
D000837:Anion Exchange Resins; D005463:Fluoroacetates; D002606:Charcoal; C014815:fluoroacetic acid; D003084:Colestipol