Toxicokinetics of bromodichloroacetate in B6C3F1 mice.
The oral and i.v. elimination kinetics were investigated for bromodichloroacetate (BDCA), a haloacetate found in drinking water. The BDCA was administered at a dose of 5, 20 and 100 mg kg-1 to B6C3F1 mice and appears to distribute to the total body water with a mean volume of distribution of 427 +/- 79 ml kg-1. It is subject to first-pass hepatic metabolism with a range of bioavailabilities of 0.28-0.73. A mean terminal half-life of 1.37 +/- 0.21 h. was calculated from the two lower doses of both i.v. and oral administration. Non-linear behavior was exhibited at doses greater than 20 mg kg-1, with a much higher than expected area under the curve (AUC), a decrease in total body clearance (CL(b)) and an increase in the terminal half-life to 2.3 h at the highest dose. The average CL(b) was 220 ml h(-1) kg-1 for the lower two doses but decreased to 156 ml h(-1) kg-1 at the high dose. The BDCA is primarily eliminated by metabolism, with only 2.4% of the parent dose being recovered in the urine at the high dose. The unbound renal clearance, as calculated from the high dose, was 15.0 ml h(-1) kg-1. The BDCA is moderately bound to plasma proteins (f(u) = 0.28) and preferentially distributes to the plasma with a blood/plasma ratio of 0.88.
Merdink
J L
JL
Graduate Program in Pharmacology and Toxicology, Washington State University, Pullman, WA 99164, USA.
Bull
R J
RJ
Schultz
I R
IR
D000085:Acetates / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D004202:Disinfectants / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D014881:Water Supply
D000085:Acetates; D004202:Disinfectants; C100580:bromodichloroacetic acid