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

Objective-To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. Animals-12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. 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 IV administration of 250 mg (f irst experiment) or 500 mg (second experiment) of furosemide. Urine was col lected hourly between 1 and 6 hours after administration of furosemide at b oth doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a fu nction of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exce eding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bo otstrap approach was used to assess the inherent variation in this estimate d probability. Results-The estimated probability of exceeding the threshold of 100 ng of f urosemide/ml and urine specific gravity < 1.012 was approximately 0% betwee n 4.0 and 5.5 hours after IV administration of 250 mg of furosemide/horse, and ranged from 0 to 1% between 4 and 5.5 hours after IV administration of 500 mg of furosemide/horse. The probability of a horse being falsely identi fied as in violation of regulatory concentrations was inversely associated with time. Conclusions and Clinical Relevance-Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that so me horses are misclassified as being in violation of regulatory concentrati ons.