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

Objective-To estimate the probability for exceeding a threshold concentrati on of furosemide commonly used for regulatory purposes after IV administrat ion of furosemide in horses. Animals-12 mature healthy horses (6 Thorough-breds 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 EL ISA. Concentration of furosemide was modeled as a function of time, account ing for inter- and intrahorse variabilities. On the basis of pharmacokineti c data, the probability for exceeding a concentration of 100 ng/ml as a fun ction of time was determined, using a semiparametric smooth functional aver aging 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 f urosemide/ml ranged from 11.6% at 4 hours to 2.2% at 5.5 hours after IV adm inistration 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 probab ility of a horse being falsely identified in violation of regulatory concen trations was inversely associated with time and positively associated with dose. Conclusions and Clinical Relevance-Interhorse variability with respect to p harmacokinetics of furosemide will result in misclassification of some hors es as being in violation of regulatory concentrations.