Comparative pharmacokinetics of meloxicam in clinically normal horses and donkeys

Melissa D. Sinclair Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, Canada, N1G 2W1.

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Katrina L. Mealey Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99163.

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Nora S. Matthews Texas Veterinary Medical Center, Texas A&M University, College Station, TX 77843.

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Ken E. Peck Texas Veterinary Medical Center, Texas A&M University, College Station, TX 77843.

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Tex S. Taylor Texas Veterinary Medical Center, Texas A&M University, College Station, TX 77843.

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Brad S. Bennett Texas Veterinary Medical Center, Texas A&M University, College Station, TX 77843.

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Abstract

Objective—To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species.

Animals—5 clinically normal horses and 5 clinically normal donkeys.

Procedures—Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables.

Results—In horses and donkeys, mean ± SD area under the curve was 18.8 ± 7.31 μg/mL/h and 4.6 ± 2.55 μg/mL/h, respectively; mean residence time (MRT) was 9.6 ± 9.24 hours and 0.6 ± 0.36 hours, respectively. Total body clearance (CLT) was 34.7 ± 9.21 mL/kg/h in horses and 187.9 ± 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VDSS) was 270 ± 160.5 mL/kg in horses and 93.2 ± 33.74 mL/kg in donkeys. All values, except VDSS, were significantly different between donkeys and horses.

Conclusions and Clinical Relevance—The small VDSS of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CLT for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CLT of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.

Abstract

Objective—To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species.

Animals—5 clinically normal horses and 5 clinically normal donkeys.

Procedures—Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables.

Results—In horses and donkeys, mean ± SD area under the curve was 18.8 ± 7.31 μg/mL/h and 4.6 ± 2.55 μg/mL/h, respectively; mean residence time (MRT) was 9.6 ± 9.24 hours and 0.6 ± 0.36 hours, respectively. Total body clearance (CLT) was 34.7 ± 9.21 mL/kg/h in horses and 187.9 ± 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VDSS) was 270 ± 160.5 mL/kg in horses and 93.2 ± 33.74 mL/kg in donkeys. All values, except VDSS, were significantly different between donkeys and horses.

Conclusions and Clinical Relevance—The small VDSS of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CLT for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CLT of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.

Nonsteroidal anti-inflammatory drugs are used for their anti-inflammatory, analgesic, antipyretic, antithrombotic, and antiendotoxic properties.1–3 There are differences in the efficacy of NSAIDs among individual animals and among species. These differences may be caused by variability in pharmacokinetics, halflife, plasma protein concentrations, and circadian rhythms; drug interactions; and renal or hepatic disease.3 Because of the large differences among the published pharmacokinetic values of meloxicam in animals, it is clear that there are marked species differences.4 This species individuality of meloxicam distribution is similar to the distributions of other NSAIDs and heightens the importance of pharmacokinetic modeling in each species prior to clinical use of a drug.

Meloxicam is an enolic acid NSAID of the oxicam group3 and is approved for use in dogs in Europe, Canada, and the United States. In small animals, meloxicam is used for the treatment of musculoskeletal injuries,5 osteoarthritis,6 and perioperative pain.7,8 In horses, NSAIDs are used primarily to treat musculoskeletal injury and minimize abdominal pain; however, they are also commonly given perioperatively for analgesia. To date, the NSAIDs that are most commonly used in equids are phenylbutazone and flunixin meglumine, which have been used in horses since the 1950s and 1970s, respectively.1 The extent and duration of the use of these 2 drugs in horses are presently reflected in numerous scientific, pharmacokinetic, and comparative pain articles.

It is now well known that there are 2 COX isoforms, COX-1 and COX-2, and that the extent of NSAID-associated inhibition of COX-1 and COX-2 activities differs depending on the drug administered.9 Most NSAIDs inhibit COX-1 and COX-2 to various degrees; however, the newer drugs including meloxicam are more selective for the COX-2 isoenzyme.3 Because of the greater COX-2 selectivity of meloxicam and other new-generation NSAIDs, these drugs may be associated with a decreased occurrence of adverse effects such as inhibition of platelet function, development of gastrointestinal tract ulcers, and impairment of renal function.9 Despite the potential advantages of meloxicam administration in equids, understanding of the pharmacokinetics of meloxicam is limited in healthy adult horses4 and, to our knowledge, nonexistent in donkeys (Equus asinus). The pharmacokinetics of several drugs have been shown to differ between horses and donkeys,10,11 but we are not aware of any published information regarding the comparative disposition of meloxicam in horses and donkeys. Therefore, the purpose of the study reported here was to determine the disposition of meloxicam (administered IV) in horses and donkeys and compare the relative pharmacokinetic variables between the species.

Materials and Methods

Animals—Five clinically normal horses (3 mares, 1 stallion, and 1 gelding) and 5 clinically normal standard donkeys (3 geldings and 2 females) were used in the study. The age of the horses ranged from 2 to 12 years (mean age, 5 years), and their weight ranged from 333 to 458 kg (mean weight, 406 kg). The age of the donkeys ranged from 12 to 15 years (mean age, 13 years), and their weight ranged from 236 to 351 kg (mean weight, 282 kg). The horses and donkeys were judged to be clinically normal on the basis of results of a physical examination, CBC, and serum biochemical analyses. Animals were acclimatized to their surroundings and allowed free access to water and hay, except during the first hour of blood collection. The study was conducted in accordance with the state guidelines of animal care, and the protocol was approved by the institutional laboratory animal use and care committee.

Experimental design and sample collection—In each horse and donkey, 1 jugular vein was catheterized with an indwelling cathetera that was secured in place. Meloxicamb (0.6 mg/kg, IV) was administered as a bolus injection into the catheterized jugular vein of each animal over a period of approximately 1 minute. The catheters were used to collect blood samples and were flushed adequately with saline (0.9% NaCl) solution containing heparin before and after sample collections. For all animals, blood samples were collected at time zero (before) and at 5, 10, 15, 20, 30, and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 24, 28, 32, 36, and 48 hours after the administration of meloxicam.

Sample analysis—Sera were obtained from the blood samples and were stored at −20°C until time of analysis. Determinations of serum meloxicam concentrations were randomized and performed in triplicate via high-performance liquid chromatographyc (similar to the method of Peck et al12). In summary, meloxicam was extracted into 2 mL of acetonitrile from 1 mL of serum containing 200 mg of NaCl and internal standard (piroxicam, 6.1 μg/mL). The limit of quantification of meloxicam was 0.1 μg/mL at 352 nm. The limit of quantification was determined by spiking serum samples at various concentrations (0.08, 0.1, and 0.12 μg/mL) with resulting values having no greater than 20% variance from the spiked value against the calibration curve. Piroxicam and meloxicam were resolved (5.7 and 7.8 minutes, respectively) on a C18 columnd with a flow rate of 0.2 mL/mL of acetonitrile with 0.19N phosphoric acid (58:42 solution). The injection volume was 15 μL. The standard curve ranged from 0.53 to 10.58 μg/mL with linear regression coefficients > 0.996. Identity of the peak was confirmed by comparison of the UV spectrum with that of an authentic standard.e Accuracy and precision were within ± 10% of actual values, and recovery was > 90% across the range of concentrations with no significant differences between species. Quality-control samples at 1.0, 3.0, and 6.0 μg/mL had within-day and between-day variation of < 6% and < 11%, respectively.

Pharmacokinetic analysis—Serum meloxicam concentration versus time data for each animal were analyzed by use of a computer software programf to estimate variables through standard noncompartmental analysis. Pharmacokinetic data, including VDSS, CLT, AUC, and MRT, were calculated for horses and donkeys by use of statistical moment theory. The equations used were as follows:

article image

Statistical analysis—The Mann-Whitney U test was used to compare the pharmacokinetic values of AUC, VDSS, CLT, and MRT between horses and donkeys. A value of P < 0.05 was considered significant.

Results

Mean ± SD serum concentration of meloxicam versus time profiles for the first 12 hours after injection was plotted for donkeys and horses (Figure 1). Pharmacokinetic variables of meloxicam after IV administration (dose, 0.6 mg/kg) were determined for each horse and donkey (Table 1). Compared with pharmacokinetic data of meloxicam in other species (pigs, humans, dogs, and cows),4 the horses of our study had a much shorter MRT (mean, 9.6 ± 9.24 hours; median, 4 hours) and greater CLT (mean, 34.7 ± 9.21 mL/kg/h; median, 38 mL/kg/h). In the donkeys, the MRT (mean, 0.6 ± 0.35 hours; median, 2.3 hours) of meloxicam was significantly shorter and CLT (mean, 187.9 ± 147.26 mL/kg/h; median, 128 mL/kg/h) was significantly greater than the values in the horses. The AUC in horses (mean, 18.8 ± 7.31 μg/mL/h; median, 16 μg/mL/h) was significantly larger than the value in donkeys (mean, 4.5 ± 2.5 μg/mL/h; median, 4.7 μg/mL/h). The VDSS of meloxicam in horses (mean, 270 ± 160.5 mL/kg; median, 185 mL/kg) was greater than the value in donkeys (mean, 93.2 ± 33.7 mL/kg; median, 88 mL/kg), but these values were not significantly different (P = 0.06). None of the animals had noticeable adverse reactions after receiving meloxicam.

Table 1—

Pharmacokinetic values for 5 horses and 5 donkeys after IV administration of a bolus of meloxicam (0.6 mg/kg).

VariableRangeMean ± SDMedian
Horses
   AUC (μg/mL/h)14–3218.8 ± 7.3116
   AUMC (μg/mL/h2)49–799233 ± 321.3469
   MRT (h)4–259.6 ± 9.244
   CLT (mL/kg/h)19–42.934.7 ± 9.2138
   VDSS (mL/kg)115–474270 ± 160.5185
Donkeys
   AUC (μg/mL/h)1–84.5 ± 2.5*4.7
   AUMC (μg/mL/h2)0.4–103.6 ± 3.692.3
   MRT (h)0.3–1.20.6 ± 0.35*0.6
   CLT (mL/kg/h)73–441187.9 ± 147.26*128
   VDSS (mL/kg)52–13193.2 ± 33.7488

Value significantly (P < 0.05) different from that in horses.

Figure 1—
Figure 1—

Mean ± SD serum meloxicam concentration as a function of time for the first 12 hours in 5 horses (closed circles) and 5 donkeys (open circles) after IV administration (time 0) of a bolus of meloxicam (0.6 mg/kg).

Citation: American Journal of Veterinary Research 67, 6; 10.2460/ajvr.67.6.1082

Discussion

Results of our study complement and extend the results of an earlier study4 of meloxicam in ponies. The pharmacokinetic disposition of meloxicam in horses was similar to findings in New Forest ponies despite the use of different pharmacokinetic software models in our analysis.4 Our investigation has also provided new data regarding the pharmacokinetics of meloxicam in donkeys and has highlighted the differences in meloxicam disposition between horses and donkeys.

The dose of meloxicam (0.6 mg/kg, IV) was chosen on the basis of an existing report4 for horses and limited clinicalg drug usage. In a study by Lees et al,4 a dose of 0.6 mg of meloxicam/kg (administered IV) was chosen because earlier preliminary work had revealed short half-lives for meloxicam in horses of 1.9 and 2.1 hours for doses of 0.2 and 0.5 mg/kg, IV, respectively (1 animal/dose group). In addition, by use of a carrageenan-sponge model of acute inflammation, that study4 revealed anti-inflammatory effects of meloxicam at a dose of 0.6 mg/kg. Therefore, we selected a dose of 0.6 mg of meloxicam/kg for administration IV to both the horses and donkeys to achieve plasma concentrations of meloxicam that were likely to have an effect against inflammation. The anti-inflammatory or analgesic effects of the plasma drug concentrations achieved at this dose were not assessed in our study, and scientific information is not currently available to quantify the minimum effective concentration for meloxicam in either species.

In the present study, the MRT of meloxicam in horses was 9.6 ± 9.24 hours and CLT was 34.7 ± 9.21 mL/kg/h. Mean residence time is a noncompartmental variable that is based on statistical moment theory and is analogous to a half-life calculation in compartmental analysis.13 In dogs, humans, and rats given clinical doses of meloxicam, MRT was 34.8, 18.2, and 18 hours and CLT was 10, 10, and 15 mL/kg/h, respectively.14 Because the clearance of meloxicam in horses in the present study was at least twice as rapid as values reported for those other species, horses may require more frequent administrations of the drug than the once-daily dose currently recommended for dogs. However, flunixin meglumine has an even faster elimination from the plasma in horses with a reported MRT of 110 ± 24.1 min and CLT of 1.1 ± 2 mL/kg/min at the standard dose of 1.1 mg/kg.11 Hence, the faster plasma elimination of meloxicam in horses may not preclude the use of this drug in equine practice. This is supported by the fact that acidic NSAIDs, including phenylbutazone, flunixin meglumine, and meloxicam, have rapid plasma clearance but relatively slow clearance from inflammatory exudates, and, therefore, may still be clinically effective as anti-inflammatory agents.4,15–17

Compared with values determined in the horses of the present study and those reported for dogs, humans, and rats, MRT (0.6 ± 0.35 h) was shorter and CLT (187.9 ± 147.26 mL/kg/h) was greater in donkeys. This suggests that meloxicam use in this species might be impractical because plasma clearance is so rapid; however, clinical trials would be necessary to evaluate effectiveness. Our results indicated that the pharmacokinetic variables of meloxicam in donkeys differed significantly from those in horses. The shorter MRT and faster plasma clearance of meloxicam in donkeys, compared with horses, are similar to findings of other comparative studies with flunixin meglumine (55 ± 7.2 min and 1.8 ± 0.5 mL/kg/min, respectively, in donkeys vs 110 ± 24.1 min and 1.1 ± 0.2 mL/kg/min, respectively, in horses)11 and phenylbutazone (1.77 ± 0.73 hours and 170 ± 54.4 mL/kg/h, respectively, in donkeys vs 3.61 ± 0.16 hours and 29 ± 4.6 mL/kg/h, respectively, in horses).10 Although it is expected that the renal clearance of meloxicam is faster in donkeys than in horses, only CLT was measured, not urine clearance; therefore, direct conclusions cannot be made.

The VDSS of NSAIDs is consistently small in most species and is attributed to the relatively high proteinbinding characteristics of these drugs, which limit their ability to reach extravascular compartments. However, protein binding was not directly measured in our study. Despite other pharmacokinetic value differences, the VDSS of meloxicam in horses (270 ± 160.5 mL/kg) of the present study was similar to that reported for flunixin meglumine (117 ± 16.4 mL/kg)11 and phenylbutazone (174 ± 12.4 mL/kg).10 In donkeys, the VDSS for meloxicam was smaller (93.2 ± 33.74 mL/kg) than the value in horses, which suggests that even more protein binding may be occurring in donkeys or that there is a relatively smaller extracellular fluid compartment in this species.14

In the present study, there was variation in pharmacokinetic values among individual animals. The values for 1 horse and 1 donkey contributed greatly to the variability in the data. In this horse, AUC was 31.8 μg/mL/h, MRT was 25.1 hours, CLT was 18.9 mL/kg/h, and VDSS was 474.1 mL/kg; in the donkey, AUC was 1.4 μg/mL/h, MRT was 0.3 hours, CLT was 441.2 mL/kg/h, and VDSS was 123.3 mL/kg. The horse was a 6-year-old Quarter Horse mare (weight, 416 kg), and the donkey was a 12-year-old standard donkey (weight, 246 kg). Both animals were healthy and were not receiving any concurrent medication. The dose of meloxicam administered and calculations were accurate for these 2 animals. There were no physical or clinicopathologic abnormalities to suggest liver or kidney disease and no plasma protein concentration abnormalities; all blood samples were collected at the same time of day to rule out circadian rhythm differences among horses and donkeys. The horse was difficult to catch for the 10and 24-hour blood sample collections, and consequently, these samples were obtained approximately 20 to 30 minutes later than scheduled. However, these sampling time difficulties cannot be expected to account for the variability in the data.

The authors recognize that additional numbers of horses and donkeys might have strengthened the pharmacokinetic data by minimizing the effects of individual variation in the data, as reflected by the large SD values. Unfortunately, assessment of additional animals was not possible at the time of our study. Hence, we have reported the findings from all animals and have elected to highlight the individual pharmacokinetic variation of 2 of these animals. Fairly large individual pharmacokinetic variability has been reported for NSAIDs and other drugs.1,3,4

The horse and donkey that appeared to be outliers with regard to the pharmacokinetic data were neither particularly old nor particularly young. The most important factors contributing to differences in drug distribution in pediatric animals, compared with older animals, are the differences in body fluid compartments and protein binding of drugs. In older animals, the major concerns are altered drug disposition and response to drugs.18 Although there appeared to be a slight difference in age between the horses (range, 2 to 12 years; mean age, 5 years) and donkeys (range, 12 to 15 years; mean age, 13 years) used in the present study, neither group consisted of truly pediatric or geriatric animals. It is difficult to speculate what effect this overall age range had on the pharmacokinetic data differences, but it may account for some of the individual variation identified within species.

Nonsteroidal anti-inflammatory drugs have an important role in the adjunctive treatment of many different inflammatory diseases as well as painful conditions. With our recent understanding of the importance of pain management and multi-modal analgesic techniques, NSAIDS are also commonly used perioperatively as analgesic agents in horses and other species. With the potential advantages of meloxicam as a newer-generation NSAID, compared with the olderclass NSAIDs such as flunixin meglumine and phenylbutazone, it would be ideal to perform trials to assess the analgesic benefits of meloxicam in clinical case management in these species. Although the findings of the present study provide pharmacokinetic data for meloxicam in horses and donkeys, further studies are required to explore the pharmacodynamics of this drug in healthy horses or donkeys or those with signs of pain that are or are not undergoing surgery. In addition, evaluation of the efficacy of meloxicam in the treatment of different types of pain (eg, visceral, musculoskeletal, or surgically induced pain) is required to assess the benefits of this drug, compared with other NSAIDs that are commonly used in these species.

ABBREVIATIONS

NSAID

Nonsteroidal anti-inflammatory drug

COX

Cyclooxygenase

VDSS

Volume of distribution at steady state

CLT

Total body clearance

AUC

Area under the serum versus time curve

MRT

Mean residence time

AUMC

Area under the first moment curve

a.

Angiocatheter-14 ga, Becton Dickinson Infusion Therapy Systems Inc, Sandy, Utah.

b.

Metacam 0.5% injection, Boehringer Ingelheim Ltd, Burlington, Ontario, Canada.

c.

HP 1090 series II diode array, Agilent Technologies, Palo Alto, Calif.

d.

Luna 5μ C18(2), 250 × 2.00 mm, Phenomenex, Torrance, Calif.

e.

Meloxicam, Sigma-Aldrich, St Louis, Mo.

f.

PKAnalyst, MicroMeth, Salt Lake City, Utah.

g.

Caron JP, Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, Mich: Personal communication, 2000.

References

  • 1

    MacAllister C. Nonsteroidal anti-inflammatory drugs: their mechanism of action and clinical use in horses. Vet Med 1994;89: 237240.

  • 2

    Livingston A. Mechanism of action of non-steroidal antiinflammatory drugs. Vet Clin North Am: Small Animl Pract 2000;30: 773804.

  • 3

    Moses VS, Bertone AL. Nonsteroidal anti-inflammatory drugs. Vet Clin North Am Equine Pract 2002;18: 2137.

  • 4

    Lees P, Sedgwick AD & Higgins AJ, et al. Pharmacodynamics and pharmacokinetics of miloxicam in the horse. Br Vet J 1991;147: 97108.

  • 5

    Cross AR, Budsberg SC, Keefe TJ. Kinetic gait analysis assessment of meloxicam efficacy in a sodium urate-induced synovitis model in dogs. Am J Vet Res 1997;58: 626631.

    • Search Google Scholar
    • Export Citation
  • 6

    Doig PA, Purbrick KA & Hare JE, et al. Clinical efficacy of meloxicam in dogs with chronic osteoarthritis. Can Vet J 2000;41: 296300.

  • 7

    Mathews KA, Pettifer G & Foster R, et al. Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery. Am J Vet Res 2001;62: 882888.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Budsberg SC, Cross AR & Quandt JE, et al. Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs. Am J Vet Res 2002;63: 15571563.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Jones CJ, Budsberg SC. Physiologic characteristics and clinical importance of the cyclooxygenase isoforms in dogs and cats. J Am Vet Med Assoc 2000;217: 721729.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Mealey KL, Matthews NS & Peck KE, et al. Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys. Am J Vet Res 1997;58: 5355.

    • Search Google Scholar
    • Export Citation
  • 11

    Coakley M, Peck KE & Taylor TS, et al. Pharmacokinetics of flunixin meglumine in donkeys, mules, and horses. Am J Vet Res 1999;60: 14411444.

  • 12

    Peck KE, Ray AC & Manuel G, et al. Quantitation of phenylbutazone in equine sera by use of high performance liquid chromatography with a nonevaporative extraction technique. Am J Vet Res 1996;57:15221524.

    • Search Google Scholar
    • Export Citation
  • 13

    Holford N, Benet L. Pharmacokinetics & pharmacodynamics: dose selection & the time course of drug action. In:Katzung B. ed.Basic & clinical pharmacology. 7th ed.Stamford, Conn: Appleton & Lange, 1998;3449.

    • Search Google Scholar
    • Export Citation
  • 14

    Busch U, Schmid J & Heinzel G, et al. Pharmacokinetics of meloxicam in animals and the relevance to humans. Drug Metab Dispos 1998;26: 576584.

  • 15

    Higgins AJ, Lees P, Taylor JB. Influence of phenylbutazone on eicosanoid levels in equine acute inflammatory exudates. Cornell Vet 1984;74: 198207.

    • Search Google Scholar
    • Export Citation
  • 16

    Lees P, Higgins AJ. Flunixin inhibits prostaglandin production in equine inflammation. Res Vet Sci 1984;37: 347349.

  • 17

    Higgins AJ, Lees P. Arachidonic acid metabolites in carrageenin induced equine inflammatory exudates. J Vet Pharmacol Ther 1984;7: 6572.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Boothe D. Factors affecting drug disposition and extrapolation of dosing regimens. In:Boothe D. ed.Small animal clinical pharmacology and therapeutics. Philadelphia: WB Saunders Co, 2001;1840.

    • Search Google Scholar
    • Export Citation
  • Figure 1—

    Mean ± SD serum meloxicam concentration as a function of time for the first 12 hours in 5 horses (closed circles) and 5 donkeys (open circles) after IV administration (time 0) of a bolus of meloxicam (0.6 mg/kg).

  • 1

    MacAllister C. Nonsteroidal anti-inflammatory drugs: their mechanism of action and clinical use in horses. Vet Med 1994;89: 237240.

  • 2

    Livingston A. Mechanism of action of non-steroidal antiinflammatory drugs. Vet Clin North Am: Small Animl Pract 2000;30: 773804.

  • 3

    Moses VS, Bertone AL. Nonsteroidal anti-inflammatory drugs. Vet Clin North Am Equine Pract 2002;18: 2137.

  • 4

    Lees P, Sedgwick AD & Higgins AJ, et al. Pharmacodynamics and pharmacokinetics of miloxicam in the horse. Br Vet J 1991;147: 97108.

  • 5

    Cross AR, Budsberg SC, Keefe TJ. Kinetic gait analysis assessment of meloxicam efficacy in a sodium urate-induced synovitis model in dogs. Am J Vet Res 1997;58: 626631.

    • Search Google Scholar
    • Export Citation
  • 6

    Doig PA, Purbrick KA & Hare JE, et al. Clinical efficacy of meloxicam in dogs with chronic osteoarthritis. Can Vet J 2000;41: 296300.

  • 7

    Mathews KA, Pettifer G & Foster R, et al. Safety and efficacy of preoperative administration of meloxicam, compared with that of ketoprofen and butorphanol in dogs undergoing abdominal surgery. Am J Vet Res 2001;62: 882888.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8

    Budsberg SC, Cross AR & Quandt JE, et al. Evaluation of intravenous administration of meloxicam for perioperative pain management following stifle joint surgery in dogs. Am J Vet Res 2002;63: 15571563.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Jones CJ, Budsberg SC. Physiologic characteristics and clinical importance of the cyclooxygenase isoforms in dogs and cats. J Am Vet Med Assoc 2000;217: 721729.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Mealey KL, Matthews NS & Peck KE, et al. Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys. Am J Vet Res 1997;58: 5355.

    • Search Google Scholar
    • Export Citation
  • 11

    Coakley M, Peck KE & Taylor TS, et al. Pharmacokinetics of flunixin meglumine in donkeys, mules, and horses. Am J Vet Res 1999;60: 14411444.

  • 12

    Peck KE, Ray AC & Manuel G, et al. Quantitation of phenylbutazone in equine sera by use of high performance liquid chromatography with a nonevaporative extraction technique. Am J Vet Res 1996;57:15221524.

    • Search Google Scholar
    • Export Citation
  • 13

    Holford N, Benet L. Pharmacokinetics & pharmacodynamics: dose selection & the time course of drug action. In:Katzung B. ed.Basic & clinical pharmacology. 7th ed.Stamford, Conn: Appleton & Lange, 1998;3449.

    • Search Google Scholar
    • Export Citation
  • 14

    Busch U, Schmid J & Heinzel G, et al. Pharmacokinetics of meloxicam in animals and the relevance to humans. Drug Metab Dispos 1998;26: 576584.

  • 15

    Higgins AJ, Lees P, Taylor JB. Influence of phenylbutazone on eicosanoid levels in equine acute inflammatory exudates. Cornell Vet 1984;74: 198207.

    • Search Google Scholar
    • Export Citation
  • 16

    Lees P, Higgins AJ. Flunixin inhibits prostaglandin production in equine inflammation. Res Vet Sci 1984;37: 347349.

  • 17

    Higgins AJ, Lees P. Arachidonic acid metabolites in carrageenin induced equine inflammatory exudates. J Vet Pharmacol Ther 1984;7: 6572.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Boothe D. Factors affecting drug disposition and extrapolation of dosing regimens. In:Boothe D. ed.Small animal clinical pharmacology and therapeutics. Philadelphia: WB Saunders Co, 2001;1840.

    • Search Google Scholar
    • Export Citation

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