Toxicokinetics of bromodichloroacetate in B6C3F1 mice

✍ Scribed by J. L. Merdink; R. J. Bull; I. R. Schultz

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 60 KB
• Volume: 21
• Category: Article
• ISSN: 0260-437X
• DOI: 10.1002/jat.732

✦ Synopsis

Abstract

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. Copyright © 2001 John Wiley & Sons, Ltd.