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Abstract

This communication reviews the matter of the clinical, pharmacological, and regulatory significance of a 4.95 nanogram/ml identification of trichlormethiazide in urine from a horse six days after administration of a compounded trichlormethiazide/ dexamethasone preparation. This combination of dexamethasone and trichlormethiazide has historically been widely used in bovine and equine medicine to reduce local inflammation and edema. The horse was administered an oral formulation of trichlormethiazide 400 mg /dexamethasone 10 mg per packet under veterinary supervision on days 7 and 6 before the race in question. Following the race, the post-race urine sample from the horse tested “positive” for trichlormethiazide at a concentration of 4.95 nanograms/ml (range 3.2 – 7.6), with no detection of trichlormethiazide in the corresponding blood sample, and no detection of the co-administered dexamethasone in either the blood or urine samples. Review of published data on post-administration blood and urine concentrations of trichlormethiazide in horses shows that 200 mg of orally administered trichlormethiazide is rapidly absorbed with blood concentrations peaking at a mean value of 35 ng/ml at 1 – 2 hours post-administration, while urinary concentrations peaked at a mean value of 6,100 ng/ml at 2 hours post-administration. Urinary concentrations of trichlormethiazide initially declined rapidly but at ten hours post-administration of a 100 mg dose of trichlormethiazide the rate of decline slowed markedly, at which point urinary concentrations of trichlormethiazide were approaching 100 ng/ml and the calculated terminal urinary half-life of trichlormethiazide in horses presented as an unusually long 189 hours. Given the 175 or so fold ratio between peak urinary and plasma concentrations of trichlormethiazide, a urinary concentration of 4.95 nanograms/ml is equivalent to a plasma concentration of trichlormethiazide of about 28 picograms/ml. On the basis that 35 ng/ml is an Effective Plasma Concentration (EPC) of trichlormethiazide, 70 pg/ml is an Irrelevant Plasma Concentration (IPC) of trichlormethiazide, which concentration is readily detectable by current drug testing technology. Given these circumstances and the possible substantial effects of urinary pH on urinary trichlormethiazide concentrations, we propose a plasma/serum concentration of 100 picograms/ml as an interim pharmacologically irrelevant plasma screening limit or “cut-off” for regulation of trichlormethiazide in equine blood serum/plasma samples.

Document Type

Article

Publication Date

2025

Digital Object Identifier (DOI)

10.21836Compendium20250603

Funding Information

This research was made possible by research support from The Equine Health and Welfare Alliance, Inc, Versailles, Kentucky, and the United States Trotting Association, Columbus, OH. Further support came from the National Institute of Food and Agriculture, U.S. Department of Agriculture, Hatch Program under project KY014066 Accession Number 7001029. Other support includes research support from The National Horsemen’s Benevolent and Protective Association and the Alabama, Arizona, Arkansas, Ontario, Canada; Charles Town, WV; Florida, Indiana, Iowa, Kentucky, Louisiana, Michigan, Minnesota, Nebraska, Ohio, Oklahoma, Oregon, Pennsylvania, Tampa Bay Downs, Florida, Texas, Washington State, and West Virginia Horsemen’s Benevolent and Protective Associations.

Funding sources provided no role in the design of the study, nor in the collection, analysis, and interpretation of all presented and referenced data.

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