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

Noah D. Cohen, Karin K. Chu, Scott D Stanley, Naisyin Wang

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 probabihty 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.

Original languageEnglish (US)
Pages (from-to)320-325
Number of pages6
JournalAmerican Journal of Veterinary Research
Volume62
Issue number3
StatePublished - Mar 2001

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furosemide
Furosemide
intravenous injection
Intravenous Administration
Horses
horses
pharmacokinetics
Pharmacokinetics
Quarter Horse
Enzyme-Linked Immunosorbent Assay
enzyme-linked immunosorbent assay

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Estimation of the probability for exceeding a threshold concentration of furosemide at various intervals after intravenous administration in horses. / Cohen, Noah D.; Chu, Karin K.; Stanley, Scott D; Wang, Naisyin.

In: American Journal of Veterinary Research, Vol. 62, No. 3, 03.2001, p. 320-325.

Research output: Contribution to journalArticle

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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 probabihty 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.",
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