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

Noah D. CohenDepartment of Large Animal Medicine & Surgery, College of Veterinary Medicine, Texas A&M University, College Station, TX 77843.

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Karin K. ChuDepartment of Statistics, College of Science, Texas A&M University, College Station, TX 77843.

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Scott D. StanleyCalifornia Veterinary Diagnostic Laboratory System, University of California, Davis, CA 95617.

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Naisyin WangDepartment of Statistics, College of Science, Texas A&M University, College Station, TX 77843.

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Abstract

Objective—To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses.

Animals—12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses).

Procedure—Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability.

Results—The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose.

Conclusions and Clinical Relevance—Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations. (Am J Vet Res 2001;62:320–325)

Abstract

Objective—To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses.

Animals—12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses).

Procedure—Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic data, the probability for exceeding a concentration of 100 ng/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess inherent variation in this estimated probability.

Results—The estimated probability of exceeding the threshold of 100 ng of furosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV administration of 250 mg of furosemide/horse and 34.2% at 4 hours to 12.3% at 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identified in violation of regulatory concentrations was inversely associated with time and positively associated with dose.

Conclusions and Clinical Relevance—Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations. (Am J Vet Res 2001;62:320–325)