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 concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses.


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


METHODS
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
Interhorse variability with respect to pharmacokinetics of furosemide will result in misclassification of some horses as being in violation of regulatory concentrations.
Cohen
N D
ND
Department of Large Animal Medicine & Surgery, College of Veterinary Medicine, Texas A&M University, College Station 77843, USA.
Chu
K K
KK
Stanley
S D
SD
Wang
N
N
D000818:Animals; D004232:Diuretics / Q000008:administration & dosage / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000662:veterinary; D005188:False Negative Reactions; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000097:blood*; D006736:Horses / Q000097:blood*; D007275:Injections, Intravenous / Q000662:veterinary; D015233:Models, Statistical; D013997:Time Factors
D004232:Diuretics; D005665:Furosemide