Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses

Abstract

Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.

Values of Urine Specific Gravity for Thoroughbred Horses Treated with Furosemide Prior to Racing Compared with Untreated Horses

“…2). This finding likely reflects the fact that there is considerable interindivdual variability in the pharmacokinetics of plasma furosemide 1 and the fact that plasma furosemide concentration and urine specific gravity are assessing related but distinct processes; plasma furosemide reflects the distribution and elimination of furosemide, whereas urine specific gravity reflects a physiologic effect of the drug on urine production. These data indicate that although urine specific gravity is significantly lowered by furosemide and that higher concentrations of serum furosemide tended to be found more commonly among horses with lower values of urine specific gravity, measure-ment of urine specific gravity alone would not be a useful test for regulating furosemide use.…”

“…1 This variability appears to be present irrespective of the testing methodology used to detect furosemide. 1 The coupled testing of urine specific gravity and serum furosemide concentration has been experimentally determined to decrease the frequency of false violators (unpublished data). These experimental findings, however, were obtained from a small group of horses that had not been exercised.…”

“…This lack of accuracy is attributable to considerable variation among horses with respect to serum concentration of drug as a function of time. 1 This variability appears to be present irrespective of the testing methodology used to detect furosemide. 1 The coupled testing of urine specific gravity and serum furosemide concentration has been experimentally determined to decrease the frequency of false violators (unpublished data).…”

“…As previously reported, raising the threshold concentration of plasma furosemide would be an effective strategy for reducing the rate of false violators of plasma furosemide regulations. 1 Raising the threshold alone, however, could be expected to increase the rate of false compliers. On the basis of the results of this and a previous study, 1 regulations that include both coupled testing of urine specific gravity and plasma or serum furosemide concentration and a threshold of furosemide concentration that is particularly high (e.g., 250 ng/ml) would improve the accuracy of furosemide testing.…”

Estimation of the probability for exceeding thresholds of urine specific gravity and plasma concentration of furosemide at various intervals after intravenous administration of furosemide in horses

“…R ecently, we reported that the estimated rate of exceeding the threshold for violation of furosemide among horses in which regulations for administration of the drug were adhered to (ie, the expected rate of false-violators, or the number of horses that receive furosemide in accordance with regulations that are falsely classified as being in violation of regulations), using the cut-point of 100 ng of furosemide/ml of serum or plasma, was relatively high. 1 In an effort to improve the accuracy of testing and to reduce the rate of false-violators, some racing jurisdictions (eg, the Texas Racing Commission) couple plasma furosemide testing with measurement of urine specific gravity. Specifically, some racing jurisdictions determine urine specific gravity of selected race entrants immediately after racing.…”