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Abstract

Objective—To describe the pharmacokinetics of phenylbutazone and oxyphenbutazone after IV administration in miniature donkeys.

Animals—6 clinically normal miniature donkeys.

Procedure—Blood samples were collected before and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after IV administration of phenylbutazone (4.4 mg/kg of body weight). Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time curve for each donkey was analyzed separately to estimate model-independent pharmacokinetic variables.

Results—Serum concentrations decreased rapidly after IV administration of phenylbutazone, and they reached undetectable concentrations within 4 hours. Values for mean residence time ranged from 0.5 to 3.0 hours (median, 1.1 hour), whereas total body clearance ranged from 4.2 to 7.5 ml/kg/ min (mean, 5.8 ml/kg/ min). Oxyphenbutazone appeared rapidly in the serum; time to peak concentration ranged from 13 to 41 minutes (mean, 26.4 minutes), and peak concentration in serum ranged from 2.8 to 4.0 mg/ml (mean, 3.5 μg/ml).

Conclusion and Clinical Relevance—Clearance of phenylbutazone in miniature donkeys after injection of a single dose (4.4 mg/kg, IV) is rapid. Compared with horses, miniature donkeys may require more frequent administration of phenylbutazone to achieve therapeutic efficacy. (Am J Vet Res 2001;62:673–675)

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses.

Animals—5 donkeys, 5 mules, and 3 horses.

Procedure—Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations. Serum concentration-time curve for each animal was analyzed separately to estimate noncompartmental pharmacokinetic variables.

Results—Clearance of trimethoprim and sulfamethoxazole in donkeys was significantly faster than in mules or horses. In donkeys, mean residence time (MRT) of sulfamethoxazole (2.5 hours) was less than half the MRT in mules (6.2 hours); MRT of trimethoprim in donkeys (0.8 hours) was half that in horses (1.5 hours). Volume of distribution at steady state (Vdss) for sulfamethoxazole did not differ, but Vdss of trimethoprim was significantly greater in horses than mules or donkeys. Area under the curve for sulfamethoxazole and trimethoprim was higher in mules than in horses or donkeys.

Conclusions and Clinical Relevance—Dosing intervals for IV administration of trimethoprim-sulfamethoxazole in horses may not be appropriate for use in donkeys or mules. Donkeys eliminate the drugs rapidly, compared with horses. Ratios of trimethoprim and sulfamethoxazole optimum for antibacterial activity are maintained for only a short duration in horses, donkeys, and mules. (Am J Vet Res 2002;63:349–353)

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in American Journal of Veterinary Research

Abstract

Objective—To investigate the effects of ketamine hydrochloride on the analgesic effects of tramadol hydrochloride in horses with signs of pain associated with naturally occurring chronic laminitis.

Animals—15 client-owned adult horses with chronic laminitis.

Procedures—Each horse received tramadol alone or tramadol and ketamine in a randomized, crossover study (≥ 2 months between treatments). Tramadol (5 mg/kg) was administered orally every 12 hours for 1 week. When appropriate, ketamine (0.6 mg/kg/h) was administered IV for 6 hours on each of the first 3 days of tramadol administration. Noninvasive systemic blood pressure values, heart and respiratory rates, intestinal sounds, forelimb load and off-loading frequency (determined via force plate system), and plasma tumor necrosis factor-α and thromboxane B2 concentrations were assessed before (baseline) during (7 days) and after (3 days) each treatment.

Results—Compared with baseline data, arterial blood pressure decreased significantly both during and after tramadol-ketamine treatment but not with tramadol alone. Forelimb off-loading frequency significantly decreased during the first 3 days of treatment with tramadol only, returning to baseline frequency thereafter. The addition of ketamine to tramadol treatment reduced off-loading frequency both during and after treatment. Forelimb load did not change with tramadol alone but increased with tramadol-ketamine treatment. Plasma concentrations of tumor necrosis factor-α and thromboxane B2 were significantly reduced with tramadol-ketamine treatment but not with tramadol alone.

Conclusions and Clinical Relevance—In horses with chronic laminitis, tramadol administration induced limited analgesia, but this effect was significantly enhanced by administration of subanesthetic doses of ketamine.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To compare plasma disposition of the R(–) and S(+) enantiomers of carprofen after IV administration of a bolus dose to donkeys and horses.

Animals—5 clinically normal donkeys and 3 clinically normal horses.

Procedure—Blood samples were collected from all animals at time 0 (before) and at 10, 15, 20, 30, and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 28, 32, and 48 hours after IV administration of a bolus of carprofen (0.7 mg/kg). Plasma was analyzed in triplicate via high-performance liquid chromatography to determine the concentrations of the carprofen enantiomers. A plasma concentration-time curve for each donkey and horse was analyzed separately to estimate noncompartmental pharmacokinetic variables.

Results—In donkeys and horses, the area under the plasma concentration versus time curve (AUC) was greater for the R(–) carprofen enantiomer than it was for the S(+) carprofen enantiomer. For the R(–) carprofen enantiomer, the AUC and mean residence time (MRT) were significantly less and total body clearance (ClT) was significantly greater in horses, compared with donkeys. For the S(+) carprofen enantiomer, AUC and MRT were significantly less and ClT and apparent volume of distribution at steady state were significantly greater in horses, compared with donkeys.

Conclusions and Clinical Relevance—Results have suggested that the dosing intervals for carprofen that are used in horses may not be appropriate for use in donkeys. (Am J Vet Res 2004;65:1479–1482)

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in American Journal of Veterinary Research

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.

Full access
in American Journal of Veterinary Research

Abstract

Objective

To compare serum disposition of flunixin meglumine after IV administration of a bolus to horses, donkeys, and mules.

Animals

3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules.

Procedure

Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after IV administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumine concentrations. The serum concentration-time curve for each horse, donkey, and mule were analyzed separately to estimate noncompartmental pharmacokinetic variables

Results

Mean (± SD) area under the curve for donkeys (646 ± 148 minute • µg/ml) was significantly less than for horses (976 ± 168 minute • μg/ml) or for mules (860 ± 343 minute • µg/ml). Mean residence time for donkeys (54.6 ± 7 minutes) was significantly less than for horses (110 ± 24 minutes) or for mules (93 ± 30 minutes). Mean total body clearance for donkeys (1.78 ± 0.5 ml/kg/h) was significantly different from that for horses (1.14 ± 0.18 ml/kg/h) but not from that for mules (1.4 ± 0.5 ml/kg/h). Significant differences were not found between horses and mules for any pharmacokinetic variable.

Conclusion and Clinical Relevance

Significant differences exist with regard to serum disposition of flunixin meglumine in donkeys, compared with that for horses and mules. Consequently, flunixin meglumine dosing regimens used in horses may be inappropriate for use in donkeys. (Am J Vet Res 1999;60:1441–1444)

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in American Journal of Veterinary Research

Abstract

Objective

To compare plasma disposition of phenylbutazone and its metabolite oxyphenbutazone after IV administration of phenylbutazone in horses and donkeys.

Animals

4 clinically normal horses and 6 clinically normal donkeys.

Procedure

Blood samples were collected from each animal at time 0 (before) and 5, 10, 20, 30, 45, 60, 90, 120, 180, 240, 300, 360, and 480 minutes after IV administration of a bolus dose of phenylbutazone. Serum was analyzed in triplicate by use of high-performance liquid chromatography for determination of phenylbutazone and oxyphenbutazone concentrations. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate model-independent pharmacokinetic variables.

Results

Significant differences were found in several pharmacokinetic variables of phenylbutazone and oxyphenbutazone in horses, compared with donkeys. Mean total body clearance of phenylbutazone in horses was fivefold less than that in donkeys (29.3 and 170.3 ml/kg/h, respectively). Mean values for area under the curve and mean residence time in horses (118.3 µg/h/ml and 3.6 hours, respectively) were significantly greater than values in donkeys (28.3 µg/h/ml and 1.7 hours, respectively). Mean values for apparent volume of distribution at steady state were not significantly different between horses and donkeys. For oxyphenbutazone, mean time to peak concentration in donkeys was significantly less than that in horses (1.6 and 6.4 hours, respectively).

Conclusion

Phenylbutazone clearance in donkeys was higher than that in horses, and appearance of the metabolite oxyphenbutazone in serum was more rapid in donkeys than in horses, indicating that hepatic metabolism of phenylbutazone is more rapid in donkeys than in horses.

Clinical Relevance

Because serum concentration of phenylbutazone after single IV bolus administration (4.4 mg/kg of body weight) decreases more rapidly in donkeys, compared with horses, phenylbutazone may require more frequent administration in donkeys to achieve therapeutic efficacy. (Am J Vet Res 1997;58:53–55)

Free access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics and clinical effects of a subanesthetic, continuous rate infusion of ketamine administered to healthy awake horses.

Animals—8 adult horses.

Procedures—Ketamine hydrochloride was administered to 2 horses, in a pilot study, at rates ranging from 0.4 to 1.6 mg/kg/h for 6 hours to determine an appropriate dose that did not cause adverse effects. Ketamine was then administered to 6 horses for a total of 12 hours (3 horses at 0.4 mg/kg/h for 6 hours followed by 0.8 mg/kg/h for 6 hours and 3 horses at 0.8 mg/kg/h for 6 hours followed by 0.4 mg/kg/h for 6 hours). Concentration of ketamine in plasma, heart rate, respiratory rate, blood pressure, physical activity, and analgesia were measured prior to, during, and following infusion. Analgesic testing was performed with a modified hoof tester applied at a measured force to the withers and radius.

Results—No signs of excitement and no significant changes in the measured physiologic variables during infusion rates of 0.4 and 0.8 mg of ketamine/kg/h were found. At 6 hours following infusions, heart rate and mean arterial pressure were decreased, compared with preinfusion measurements. An analgesic effect could not be demonstrated during or after infusion. Pharmacokinetic variables for 0.4 and 0.8 mg/kg/h infusions were not significantly different.

Conclusions and Clinical Relevance—Ketamine can be administered to awake horses at 0.4 or 0.8 mg/kg/h without adverse behavioral effects. The observed pharmacokinetic values are different than those reported for single-dose IV bolus administration of this drug.

Full access
in American Journal of Veterinary Research

SUMMARY

Objective

To determine the cardiovascular effects of buprenorphine in isoflurane-and halothane-anesthetized dogs.

Animals

6 healthy adult hound-type dogs given buprenorphine (16 μg/kg of body weight, IV) or isovolumetric 5% dextrose solution during anesthesia with isoflurane or halothane.

Procedure

Each dog was anesthetized 4 times, with a minimum of 10 days between episodes. Anesthesia was induced with isoflurane or halothane in O2 by mask, and was maintained with 1.9% isoflurane or 1.3% halothane (end-tidal concentration). The Paco2 was maintained between 35 and 45 mm of Hg by use of mechanical ventilation, and the following variables were determined: systolic, diastolic, and mean arterial blood pressures; cardiac output; cardiac index; stroke volume; heart rate; systemic vascular resistance; mean pulmonary arterial pressure; and pulmonary vascular resistance. In addition, arterial blood samples for gas and acid-base analyses were collected at 30-minute intervals for 2.5 hours. After baseline values were recorded, dogs were randomly assigned to receive either buprenorphine (16 μg/kg, IV) or isovolumetric 5% dextrose solution. All variables were then recorded at 15-minute intervals for 2.5 hours.

Results

During isoflurane anesthesia, buprenorphine administration caused significant (P < 0.05) reductions in diastolic arterial pressure, mean arterial pressure, systolic arterial pressure, cardiac index, and heart rate, whereas systemic vascular resistance increased significantly. During halothane anesthesia, buprenorphine administration caused significant decreases in heart rate, cardiac index, mean, systolic and diastolic arterial blood pressures, and stroke volume, whereas pulmonary arterial blood pressure and systemic vascular resistance increased significantly.

Conclusion

Although the changes seen were significant, they were not sufficiently large to be of clinical importance in healthy dogs. (Am J Vet Res 1997;58:1280–1284)

Free access
in American Journal of Veterinary Research