Effect of body weight on the pharmacokinetics of flunixin meglumine in miniature horses and quarter horses

Abstract

In most species, large variations in body size necessitate dose adjustments based on an allometric function of body weight. Despite the substantial disparity in body size between miniature horses and light-breed horses, there are no studies investigating appropriate dosing of any veterinary drug in miniature horses. The purpose of this study was to determine whether miniature horses should receive a different dosage of flunixin meglumine than that used typically in light-breed horses. A standard dose of flunixin meglumine was administered intravenously to eight horses of each breed, and three-compartmental analysis was used to compare pharmacokinetic parameters between breed groups. The total body clearance of flunixin was 0.97 ± 0.30 mL/min/kg in miniature horses and 1.04 ± 0.27 mL/min/kg in quarter horses. There were no significant differences between miniature horses and quarter horses in total body clearance, the terminal elimination rate, area under the plasma concentration versus time curve, apparent volume of distribution at steady-state or the volume of the central compartment for flunixin (P > 0.05). Therefore, flunixin meglumine may be administered to miniature horses at the same dosage as is used in light-breed horses.

In vitro anti‐LPS dose determination of ketorolac tromethamine and in vivo safety of repeated dosing in healthy horses

“…A similar study investigating the pharmacokinetics of KT at 0.5 mg/kg IV administered prior to castration in horses reported a relatively high LOQ (0.01 μg/ml) that did not allow comparison to the low (< 0.01 μg/ml) plasma drug concentrations we observed at 4, 8, and 12 hr (Ferraresi et al., ). Mean plasma drug concentrations of FM were similar to previous pharmacokinetic studies investigating the same dosage used here (1.1 mg/kg IV) in healthy adult horses (Foreman et al., ; Lee & Maxwell, ; Semrad et al., ; Toutain, Autefage, Legrand, & Alvinerie, ). As the therapeutic concentration of KT has not been elucidated in horses, the significance of the observed difference in plasma drug concentrations between FM and KT is unknown.…”

Pharmacokinetics and effects on thromboxane B2production following intravenous administration of flunixin meglumine to exercised thoroughbred horses

“…There are a number of previous reports describing the pharmacokinetics of flunixin following i.v. administration in the horse (Semrad et al ., ; Soma et al ., ; Jensen et al ., ; Coakley et al ., ; Lee & Maxwell, ). With respect to regulatory samples, however, only one of the aforementioned studies (Lee & Maxwell, ) utilized instrumentation sensitive enough to measure flunixin concentrations at or below the current ARCI recommended regulatory threshold and in that study sampling was terminated 24 h postdrug administration.…”

“…administration in the horse (Semrad et al ., ; Soma et al ., ; Jensen et al ., ; Coakley et al ., ; Lee & Maxwell, ). With respect to regulatory samples, however, only one of the aforementioned studies (Lee & Maxwell, ) utilized instrumentation sensitive enough to measure flunixin concentrations at or below the current ARCI recommended regulatory threshold and in that study sampling was terminated 24 h postdrug administration. As previous reports describing the pharmacokinetics of flunixin either used less sensitive analytical instrumentation or described plasma or serum concentrations for a shorter period of time than is necessary to establish when levels no longer exceed the regulatory threshold, these studies are not particularly amenable to establishing withdrawal times for the 20 ng/mL regulatory threshold.…”

Anatomical and physiological basis for the allometric scaling of cisplatin clearance in dogs

“…In humans and many domestic animal species, the variation in adult body weight is narrow, limiting allometric effects. Dogs and horses are two domesticated animals in which a wide range of body weights occur, but allometric effects on drug disposition have not been reported in horses (Lee & Maxwell, ). Allometric scaling is useful for extrapolations employing both interspecies and intraspecies allometric scaling, if a species varies widely in body size (Ritschel et al ., ; Mahmood, ).…”

“…In humans and many domestic animal species, the variation in adult body weight is narrow, limiting allometric effects. Dogs and horses are two domesticated animals in which a wide range of body weights occur, but allometric effects on drug disposition have not been reported in horses (Lee & Maxwell, 2014). Allometric scaling is useful for extrapolations employing both interspecies and intraspecies allometric scaling, if a A = coefficient of the distribution phase, B = coefficient of the elimination phase, k 10 = elimination rate constant; a = rate constant of distribution half-life (t 1/2(a) ); b= rate constant of elimination half-life (t 1/2(b) ) ; V ss = apparent volume of distribution at steady-state; AUC = area under the plasma drug concentration-time curve, extrapolated to infinity; CL total = total body clearance; CL renal = renal clearance; % urinary excretion = percentage of the total cisplatin dose recovered from urine over 72 h. (Ritschel et al, 1992;Mahmood, 2007).…”