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Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

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 (> 0.05). Therefore, flunixin meglumine may be administered to miniature horses at the same dosage as is used in light-breed horses.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

The miniature horse breed has increased in popularity over the last 30 years. There have been multiple recent publications demonstrating the unique medical predilections of the breed, including an increased propensity for fecalith obstructions (Haupt et al., 2008), tracheal collapse (Aleman et al., 2008), lateral patellar luxation (Engelbert et al., 1993) and hypertriglyceridemia (Waitt & Cebra, 2009). Despite these developments, to the authors' knowledge, there have been no studies evaluating appropriate drug dosing in miniature horses.

The large difference in body size between miniature horses and standard-sized horses suggests the need to take body size into account when dosing miniature horses. When there is considerable variation in body size among animals of the same (Maxwell & Jacobson, 2008; Martinez et al., 2009) or different species (Mahmood et al., 2006; Huh et al., 2011), pharmacokinetic parameters such as clearance and elimination half-life relate to body weight in a nonproportional manner (Mordenti, 1986; Ritschel et al., 1992). In general, smaller individuals have a higher surface area to volume ratio and a higher mass-specific metabolic rate. As a consequence, faster drug clearance and shorter elimination half-life occur in smaller-sized individuals, necessitating higher drug doses on a body weight normalized, or mg/kg basis, as compared to larger-sized individuals (Mordenti, 1986; Maxwell & Jacobson, 2008). This phenomenon is perhaps best recognized in the dosing of cytotoxic anticancer drugs, which is based on the nonproportional relationship between body surface area and body weight (Frazier & Price, 1998; Sparreboom, 2005; Loos et al., 2006). However, nonproportional drug disposition is also observed in numerous drug classes aside from anticancer drugs. Within the Equus genus, the clearance of phenylbutazone is much faster in miniature donkeys than is reported in standard donkeys (Matthews et al., 2001). Additionally, the clearance of phenolsulfonphthalein is faster in ponies than in light-breed horses (Hinchcliff et al., 1987). To the author's knowledge, there have been no studies comparing the disposition of any drug among the weight categories of the horse. If drug disposition is nonproportional among horses of greatly different body weights, then therapeutic regimens in horses could be made safer and more effective by better defining the relationship between body size and drug disposition.

Flunixin meglumine is a nonsteroidal anti-inflammatory drug used commonly in equine practice. In a recent survey of the American Association of Equine Practitioner member veterinarians, 91% of respondents prescribe it at least weekly (Hubbell et al., 2010). In addition to its use as a pain reliever, it is also used to inhibit the systemic effects of endotoxemia (Bryant et al., 2003). Potential toxicities associated with nonsteroidal anti-inflammatory drugs include right dorsal colitis, oral and gastric ulceration, and nephrotoxicity (Black, 1986; McConnico et al., 2008; Videla & Andrews, 2009). Because of these factors, it is important to ensure that dose recommendations for this drug are both efficacious and pose a minimal risk of toxicity.

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 and, in so doing, form a basis for future studies addressing dose recommendations in the miniature horse. The study hypothesis was that the total body clearance of flunixin would be faster in miniature horses as compared to quarter horses.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

Horses

Sixteen clinically healthy horses, consisting of quarter horse type horses (n = 8) and miniature horses (n = 8), were used in this study. Horses in each breed group were similar with respect to gender, age and body condition score, but body weights were approximately fivefold different between the two groups (Table 1). Horses were determined to be healthy by physical examination by a veterinarian, and a veterinarian assessed body condition score of each horse, using a nine-point system (Henneke et al., 1983). Horses were housed in their usual environment or in individual stalls with free access to water and hay during the study. The study protocol was approved by the Oklahoma State University Animal Care and Use Committee, and written informed consent was obtained for the four quarter horses and eight miniature horses that were privately owned. The remaining four quarter horses were maintained as part of a University owned teaching herd.

Table 1. Summary of demographic data for horses employed in the present study
 Quarter horsesMiniature horsesP value
  1. Data are expressed as the mean, followed by the range.

Age (year)7 (3–12)6 (3–12)0.63
Weight (kg)489 (420–559)100 (82–126)<0.001
Body condition score5.7 (5.3–6.3)5.5 (4.7–6.7)0.50
Gender1.0
Gelding44 
Mare44

Drug administration

A commercial formulation of flunixin meglumine (Flunixiject; Butler Schein Animal Health, Dublin, OH, USA) was administered as an intravenous bolus via an indwelling 14 gauge catheter placed in the right jugular vein using an aseptic technique. A dose of approximately 1.1 mg/kg was calculated for each horse such that an accurate volume could be measured using standard syringes.

Blood collection

Baseline plasma samples were collected from all horses prior to drug administration. Following intravenous administration of flunixin meglumine, 6 mL blood samples were collected via a separate 14 gauge catheter previously placed in the opposite jugular vein at 3, 6, 10, 20 and 40 min and at 1, 2, 3, 4, 6, 8, 10, 12 h. Further sampling was performed by jugular venipuncture at 24 h after the administration of flunixin. All samples were collected into heparinized blood collection tubes and placed immediately into an ice water bath. Samples were then centrifuged within 1 h of collection, and plasma was separated and stored at −80 °C until assayed.

Flunixin assay

A novel assay utilizing high-performance liquid chromatography (HPLC) with ultraviolet detection was developed for the sensitive and specific determination of plasma flunixin concentrations in equine plasma. The HPLC system consisted of a ProStar™ 210 pump, 410 autosampler and 285 nm ultraviolet detector (Varian Medical Systems, Palo Alto, CA, USA). A reversed-phase column and guard column (Symmetry™ C18, 5 μm, 4.6 × 150 mm; Waters Corporation, Milford, MA, USA) were utilized at 30 °C for analyte separation. Mobile phase components were prepared fresh daily and consisted of 1.5% acetic acid and 10% acetonitrile in water (mobile phase A) and 1.5% acetic acid and 90% acetonitrile in water (mobile phase B). Stock solutions were prepared by adding flunixin (Sigma-Aldrich, St. Louis, MO, USA) or the internal standard, niflumic acid (Sigma-Aldrich), to methanol. Plasma calibrants were prepared at concentrations of 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2.5, 5, 10, 15 and 30 μg/mL using flunixin stock solutions and heparinized plasma from unmedicated horses. Calibrants and quality control samples were prepared by adding 950 μL of unmedicated equine heparinized plasma to 50 μL of the appropriate calibrant or quality control solution, followed by vortex mixing. Calibrant curves were constructed from the ratio of flunixin/niflumic acid and were weighted using the reciprocal of the flunixin concentration. Criteria for acceptance of each run included that a minimum of five calibrators back-calculated to within 15% of the nominal concentration and that the coefficient of determination was >0.99. All calibrators that met the acceptance criteria were included in the calibration curve associated with each run, and calibration samples always bracketed the experimentally determined flunixin concentrations. One millilitre of 2% phosphoric acid containing niflumic acid at a concentration of 4 μg/mL was added to each 1 mL plasma sample and vortex mixed. Liquid–liquid extraction was performed via the addition of 10 mL of diethyl ether. End-over-end mixing for 15 min was followed by centrifuging for 10 min. The supernatant was aspirated and dried under nitrogen for 20 min at 30 °C. The residue was dissolved in 200 μL of mobile phase, and 50 μL was injected onto the column. The mobile phase consisted of 60% ‘A’ and 40% ‘B’ with isocratic flow at 1 mL/min. Flunixin eluted at approximately 10 min and niflumic acid at approximately 20.5 min. Recovery estimates were performed in plasma using six replicates. Intraday accuracy and coefficient of variation estimates were performed in plasma using three replicates. Interday accuracy and coefficient of variation estimates were performed in plasma using three replicates on three separate days. The limit of quantification was estimated using six replicates and was defined as the lowest concentration associated with a tenfold signal/noise ratio. The limit of detection was estimated using three replicates and was defined as the concentration at which signal/noise was at least threefold.

Pharmacokinetic analysis

Plasma flunixin concentrations following intravenous administration of flunixin meglumine were analysed compartmentally using kinetica™ software version 5.0 (Thermo Fisher Scientific, Philadelphia, PA, USA). Intravenous data for each horse were fit to the following equation:

  • display math

Data were weighted by the reciprocal of the plasma flunixin concentration and were fit to standard compartmental models. Total body clearance was calculated as the product of the volume of the central compartment (Vc) and the rate of elimination from the central compartment (k10). The most appropriate model was selected using Akaike's information criterion and the Schwarz criterion, and standard compartmental equations were then used to estimate the pharmacokinetic parameters for each horse. The mean and standard deviation for each group (miniature horses and quarter horses) were estimated for each pharmacokinetic parameter.

Allometric comparisons

The total body clearance for flunixin determined in miniature horses was compared with that predicted by standard allometry, as has been reported previously (Mordenti, 1986). The general form of the allometric equation used for scaling of pharmacokinetic parameters was the following:

  • display math

where y is flunixin clearance; BW is the body weight; a is the allometric coefficient and b is the allometric exponent. The allometrically predicted flunixin clearance in miniature horses was calculated from the quarter horse clearance data by solving for the mass coefficient in the equation above and setting = 0.75, as is frequently used in standard allometric calculations and is arguably a universal scaling exponent across species (Hu & Hayton, 2001). The values of log10 total body clearance were regressed against log10 body weight and compared with the curve predicted by standard allometry.

Statistical analysis

A Wilcoxon rank-sum test was used to analyse the difference in body condition score between the groups, whereas a two-sample t-test was used to test whether age differed between quarter horses and miniature horses. Two-sample Student's t-tests were used to test the difference in selected pharmacokinetic parameters: mass normalized clearance (Cl), elimination phase rate constant (γ), area under the plasma concentration versus time curve (AUC), apparent volume of distribution at steady-state (Vd(ss)) and volume of the central compartment (Vc). Significance was set at α = 0.05. Statistical calculations were performed using sigmaplot software version 11.0 (Systat Software, Inc., Chicago, IL, USA).

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

Assay

At fortified plasma flunixin concentrations of 0.075, 5 and 12.5 μg/mL, recovery of flunixin was 86 ± 5%, 86 ± 2% and 85 ± 3%, respectively. At a plasma concentration of 4.0 μg/mL, recovery of niflumic acid was similar to that of flunixin at 83 ± 3%. Intraday accuracy of the assay at 0.075, 3.75 and 12.5 μg/mL was 99%, 93%, and 92%, respectively. Intraday coefficient of variation at 0.075, 3.75 and 12.5 μg/mL was 1%, 2% and 2%, respectively. Interday accuracy at 0.075, 3.75 and 12.5 μg/mL was 99%, 96% and 91%, respectively. Interday coefficient of variation at 0.075, 3.75 and 12.5 μg/mL was 3%, 2% and 1%, respectively. The limit of quantification, 0.025 μg/mL, was associated with good accuracy and precision, with an accuracy of 93% and a coefficient of variation of 11%. The limit of detection was 0.00625 μg/mL. The assay provided good separation of flunixin and the internal standard from endogenous plasma constituents, even at low plasma flunixin concentrations (Fig. 1).

image

Figure 1. Chromatograms of unmedicated equine plasma (grey line) and equine plasma with an estimated flunixin concentration of 0.15 μg/mL (black line), sampled at 12 h after administration of flunixin meglumine. IS, internal standard.

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Quantification of flunixin

All horses tolerated the administration of a single dose of flunixin meglumine well, with no adverse effects noted for the duration of the study. In addition to sampling times described above, additional sampling was performed at 36 h in the first three quarter horses and the first three miniature horses studied, but flunixin could not be detected in any of these six samples. Thereafter, collection of the 36-h postadministration sample was discontinued. Flunixin concentrations rapidly declined after intravenous administration, followed by a slower distribution phase and then an extended elimination phase; flunixin could be quantified for at least 12 h in all horses and for 24 h in five of eight quarter horses and four of eight miniature horses (Fig. 2).

image

Figure 2. Mean (±SEM) plasma concentrations of flunixin after i.v. administration of flunixin meglumine at a dosage of 1.1 mg/kg to eight miniature horses and eight quarter horses. Flunixin concentrations were similar between the two groups throughout the sampling period.

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Pharmacokinetics

The most appropriate compartmental model for pharmacokinetic analysis was determined to be a three-compartment model in all horses (Table 2). There were no significant differences between groups in clearance (P = 0.66), elimination phase rate constant (= 0.44), AUC (= 0.51), Vd(ss) (= 0.89) or the Vc (= 0.49). In addition, the mass specific clearance of flunixin was not related to body weight (Fig. 3a).

Table 2. Comparison of pharmacokinetic parameters for flunixin after Intravenous (i.v.) administration to quarter horses and miniature horses
ParameterQuarter horsesMiniature horses
  1. Values are expressed as mean or *harmonic mean ± SD (range) (Lam et al., 1985).

  2. Dose, dose administered; C0, serum drug concentration at time 0; A, coefficient of rapid distribution phase; B, coefficient of slow distribution phase; C, coefficient of elimination phase; t1/2α, rapid distributional half-life; t1/2β, slow distributional half-life; t1/2γ, terminal elimination phase half-life; t1/2k10, elimination half-life; k10, first-order rate constant for elimination from the central compartment; other intercompartmental rate constants follow similar nomenclature; Vc, apparent volume of the central compartment; Vd(ss), apparent volume of distribution at steady-state; Vd(area), apparent volume of distribution by area; Cl, total body clearance; AUC, Area under the plasma concentration versus time curve, extrapolated to infinity; MRT, mean residence time.

Dose (mg/kg BW)1.10 ± 0.02 (1.07–1.14)1.11 ± 0.02 (1.08–1.13)
C0 (μg/mL)19.8 ± 2.7 (17.3–25.2)19.1 ± 3.4 (14.7–23.1)
A (μg/mL)9.9 ± 2.1 (7.4–13.5)9.7 ± 1.9 (7.5–12.2)
B (μg/mL)8.3 ± 0.8 (7.2–9.5)6.6 ± 1.1 (4.7–7.7)
C (μg/mL)1.6 ± 1.1 (0.5–3.5)2.8 ± 2.3 (0.4–8.2)
t1/2α (h)0.07 ± 0.01 (0.05–0.08)0.08 ± 0.02 (0.05–0.10)
t1/2β (h)0.81 ± 0.18 (0.57–1.11)0.79 ± 0.21 (0.53–1.13)
t1/2γ (h)3.38 ± 1.14 (2.06–6.03)2.96 ± 1.00 (2.14–5.98)
t1/2k10 (h-1)0.62 ± 0.16 (0.47–1.17)0.70 ± 0.22 (0.47–1.45)
k10 (h-1)1.1 ± 0.3 (0.6–1.5)1.0 ± 0.3 (0.5–1.5)
k12 (h-1)3.9 ± 0.7 (3.3–5.5)3.5 ± 1.1 (2.7–6.2)
k21 (h-1)5.3 ± 0.6 (4.6–6.6)4.7 ± 1.2 (3.6–6.9)
k13 (h-1)0.3 ± 0.1 (0.2–0.5)0.3 ± 0.1 (0.2–0.4)
k31 (h-1)0.3 ± 0.1 (0.1–0.6)0.4 ± 0.2 (0.1–0.9)
Vc (L/kg BW)0.056 ± 0.007 (0.042–0.063)0.059 ± 0.011 (0.048–0.074)
Vd(ss) (L/kg BW)0.157 ± 0.022 (0.119–0.183)0.159 ± 0.039 (0.095–0.216)
Vd(area) (L/kg BW)0.324 ± 0.104 (0.182–0.507)0.279 ± 0.149 (0.111–0.621)
Cl (mL/min/kg BW)1.04 ± 0.27 (0.60–1.48)0.97 ± 0.30 (0.47–1.20)
AUC (μg·h/mL)18.8 ± 5.5 (12.4–30.8)21.3 ± 9.2 (14.0–39.6)
MRT (h)2.7 ± 0.7 (1.8–3.7)3.0 ± 1.3 (1.7–5.9)
image

Figure 3. Relationship between flunixin clearance and body weight. (a) Mass specific clearance of flunixin versus body weight in miniature horses and quarter horses, demonstrating that total body clearance was similar between the two groups when normalized to body weight. (b) Total body clearance of flunixin versus body weight in miniature horses and quarter horses, showing that total body clearance varied proportionally with body weight. The regression line calculated from the data (solid line) is compared with that predicted from standard allometry (dashed line).

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Allometric comparison

The regression curve relating measured total body clearance to body weight was associated with a mass exponent of approximately unity:

  • display math

The 95% confidence interval (0.82, 1.26) for the calculated mass exponent did not contain the three quarters exponent predicted by the principles of standard allometry (Fig. 3b). If the clearance of flunixin in miniature horses had varied allometrically from that of quarter horses by the three quarters mass exponent, then the predicted flunixin clearance in the miniature horses would have been 1.56 mL/min/kg BW, more than 50% greater than the measured clearance of 0.97 mL/min/kg BW. The statistical power (β) of this study to detect such a difference was 0.95, with SD = 0.27 and α = 0.05. The other pharmacokinetic parameters tested, including the elimination rate, AUC, Vd(ss) and Vc, were similarly unrelated to body weight (elimination rate and AUC) or were directly proportional to body weight (Vd(ss), Vc; data not shown).

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References

The novel flunixin assay employed in the present study allowed the sensitive and specific determination of flunixin concentrations in equine plasma. The sensitivity of this method was improved as compared to previously reported HPLC methods, with the limit of detection of 0.00625 μg/mL lower than previous reports of 0.05 μg/mL (Semrad et al., 1985; Higgins et al., 1987) and the limit of quantification of 0.025 μg/mL lower than previous reports of 0.05 μg/mL (Soma et al., 1988). Although the two-compartment model describing flunixin pharmacokinetics in horses predominates in the literature (Chay et al., 1982; Semrad et al., 1985; Lees et al., 1987; Soma et al., 1988), the sensitivity of the present study allowed for the first time the reliable quantification of flunixin for up to 24 h after administration. The longer detection time demonstrated the presence of a third compartment, which was confirmed by the Akaike's information criterion and the Schwarz criterion in all horses. The stated accuracy, precision and recovery of the novel assay were also well within acceptable limits. As this was the first description of this specific method for analysis of flunixin in equine plasma, the method was deemed robust and feasible for future pharmacokinetic studies.

The pharmacokinetic parameters calculated in the present study for light-breed horses were similar when compared with those in previous studies (Lees et al., 1987; Coakley et al., 1999). Specifically, the calculated mass specific clearance of flunixin in light-breed horses of 1.04 ± 0.27 mL/min/kg BW was very similar to the clearance of 1.1 ± 0.2 mL/min/kg BW (Coakley et al., 1999) reported previously in light-breed horses given the same dose of flunixin. Low variability in the kinetics of flunixin was observed among horses in the present study, demonstrating that flunixin pharmacokinetics are generally predictable, even within these two disparate breeds of horses.

An acknowledged shortcoming of this study was the lack of any samples taken between the 12 and 24 h time points. The study was designed in this fashion to encourage the participation of privately owned horses. The inclusion of 16- and 20-h postadministration samples would have improved the definition of the third compartment. To investigate the possibility that sampling times affected the calculation of the key parameters under investigation, the pharmacokinetic analysis was repeated on the plasma flunixin versus time data truncated at the 12-h time point, when all horses had quantifiable plasma flunixin concentrations. The elimination rate constant was not substantially affected by this truncated analysis, and the significance of the comparisons did not change. For example, the terminal phase elimination rates in quarter horses and miniature horses with inclusion of quantifiable 24 h time points were 0.20 and 0.23 per hour, respectively. When the data were truncated at 12 h, the terminal phase elimination rates in quarter horses and miniature horses were 0.25 and 0.24 per hour, respectively. Therefore, the selected sampling time points did not appear to play an important role in the outcome of the study.

Physiological parameters such as metabolic rate, hepatic blood flow, glomerular filtration rate and body surface area can all be described as a nonproportional, or allometric, function of body weight when there is a large amount of size variation (Prothero, 1982, 1984). Because of this allometric relationship, pharmacokinetic parameters and therefore drug dosages also scale allometrically with body weight (Mordenti, 1986; Ritschel et al., 1992). This is described most extensively between species, or interspecifically (Mahmood et al., 2006; Huh et al., 2011). However, intraspecific allometric scaling, or allometry within a single species, becomes important when there is considerable variation in body weight among adults within the species (Maxwell & Jacobson, 2008; Martinez et al., 2009).

The large variation in body size within the equine species led the authors to hypothesize that flunixin would follow an allometric relationship in the horse, as has been reported for phenylbutazone clearance in miniature donkeys as compared to full-sized donkeys (Matthews et al., 2001). However, the results of the present study in miniature horses did not demonstrate a breed-related effect on the disposition of flunixin. Statistical comparisons between breed groups were performed on those pharmacokinetic parameters used commonly in allometric calculations and deemed clinically relevant to dose calculations (Cox et al., 2004; Dinev, 2008; Gebru et al., 2011). These key pharmacokinetic parameters for flunixin showed no significant differences between miniature horses and quarter horses. Furthermore, the present data did not support a nonproportional, or allometric, relationship between flunixin disposition and body weight in the horse.

For species in which standard allometry is followed, drug clearance is proportional to body weight raised to the 3/4 power on a double log10 plot (Fig. 3b). The range in equine body weights utilized in the present study was sufficient to detect an allometric effect on flunixin clearance, if the horses had indeed followed standard allometry as we initially hypothesized. It was also possible that flunixin clearance followed a scaling factor other than the 3/4 power, such as the 2/3 power commonly utilized in body surface area calculations (Gouma et al., 2012). Therefore, flunixin clearance was also plotted against body weight on a double log10 plot to examine the possibility of a nonproportional relationship. However, the mass exponent of that comparison was very similar to unity, further demonstrating the absence of any allometric effect. Other pharmacokinetic parameters (elimination rate, AUC and volumes of distribution) that were subject to allometric effects in previous studies failed to vary nonproportionally with body weight in the present study in horses. Therefore, the present data do not support adjustment of the dosage of flunixin meglumine in miniature horses for pharmacokinetic reasons.

Although the efficacy and toxicity of flunixin have not been compared between breeds, the relationship between the pharmacokinetics and pharmacodynamics of flunixin has been well described in the horse (Toutain et al., 1994; Landoni & Lees, 1995; Lees et al., 2004). For example, an intravenous dose of 1 mg/kg was predicted to have near maximal effects on the pharmacodynamic endpoints of local skin temperature, stride length, rest angle flexion, maximal carpal flexion and circumference of the inflamed joint for 2–10 h after administration (Toutain et al., 1994). The majority of these effects depended upon flunixin plasma concentration (Lees et al., 2004). Therefore, it is likely that the pharmacokinetic similarity between miniature horses and quarter horses will permit the same dosage to be used in both breeds with similar effects.

While the present results do not support a need to adjust the dosage for flunixin administration to miniature horses, drugs that are subject to different routes of elimination might be subject to size effects on drug disposition. Flunixin is a highly protein bound drug that is metabolized in the liver but is not avidly extracted, characteristics that may be associated with poor correlation between body weight and drug clearance when compared across species (Riviere et al., 1997). Indeed, a compilation of interspecific allometric data from 44 different drugs across multiple veterinary species reported that the elimination half-life of flunixin did not correlate with body weight, with a coefficient of determination of 0.40 (Riviere et al., 1997). In contrast, the same study reported that elimination half-life was significantly correlated with body weight in drugs cleared via glomerular filtration such as carbenicillin, tetracycline, cephapirin, apramycin, chlortetracycline, gentamicin and ampicillin (Riviere et al., 1997). Future studies with these drugs may be more likely to show allometric scaling within the equine species, and it is possible that they would require dose adjustments for use in miniature horses.

There is a current perception by both horse owners and veterinarians that miniature horses are more likely to experience toxicity from nonsteroidal anti-inflammatory drugs (NSAIDs) than are light-breed horses (Mogg, 2012). Such evidence is primarily anecdotal and likely represents overdosage of NSAIDs in miniature horses when their smaller body weight is not taken into account, a situation observed previously in a case referred to this institution (Lyndi Gilliam, personal communication). The absence of objective studies investigating the pharmacokinetics of any veterinary drug in miniature horses has required the veterinary practitioner to use only subjective information to support therapeutic decisions in this unique breed. Although it remains imperative to adjust drug doses to body weight when administering therapeutics to miniature horses, the results of the present study allow practitioners to more confidently administer flunixin meglumine to miniature horses using typical equine dosing regimens.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. References
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