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.


METHODS
12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares.


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 IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were determined by use of an ELISA. Concentration of furosemide and urine specific gravity was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis of pharmacokinetic and specific gravity data, the probability of exceeding a concentration of 100 ng of furosemide/ml as a function of time was determined, using a semiparametric smooth functional averaging method. A bootstrap approach was used to assess the inherent variation in this estimated probability.


RESULTS
The estimated probability of exceeding the threshold of 100 ng of furosemide/ml and urine specific gravity < 1.012 was approximately 0% between 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 identified as in violation of regulatory concentrations was inversely associated with time.


CONCLUSIONS
Coupling plasma furosemide concentration with urine specific gravity testing will greatly reduce the chance that some horses are misclassified as being in violation of regulatory concentrations.
Chu
K K
KK
Department of Statistics, College of Science, Texas A&M University, College Station 77843-4475, USA.
Cohen
N D
ND
Stanley
S D
SD
Wang
N
N
D000818:Animals; D004232:Diuretics / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D005189:False Positive Reactions; D005260:Female; D005665:Furosemide / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D006736:Horses / Q000097:blood / Q000378:metabolism* / Q000652:urine; D007275:Injections, Intravenous / Q000662:veterinary; D012044:Regression Analysis; D013046:Specific Gravity / Q000187:drug effects; D014556:Urine / Q000737:chemistry
D004232:Diuretics; D005665:Furosemide