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in Journal of the American Veterinary Medical Association
in Journal of the American Veterinary Medical Association

Abstract

Objective

To compare pharmacokinetics of eltenac after first and last IV administrations (0.5 mg/kg), using a multiple dosing schedule.

Animals

6 adult mares.

Procedure

Eltenac (50 mg/ml) was administered IV at a dosage of 0.5 mg/kg of body weight every 24 hours for days 0 through 4. On days 0 and 4, blood samples were collected before, then periodically for 8 hours after eltanac administration. Concentration of eltenac in plasma samples was determined by use of high-performance liquid chromatography.

Results

On day 0, median area under the plasma eltenac concentration versus time curve (AUC) was 6.77 μg•h/ml (range, 5.61 to 8.08 μg•h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.03 to 1.40 ml/min/kg), and median steady-state volume of distribution was 191 ml/kg (range, 178 to 218 ml/kg). Median terminal half-life of eltenac was 2.36 hours (range, 2.30 to 2.98 hours). On day 4, median eltenac AUC was 6.70 μg•h/ml (range, 5.21 to 7.44 μg•h/ml), median plasma clearance was 1.23 ml/min/kg (range, 1.12 to 1.53 ml/min/kg), and median steady-state volume of distribution was 193 ml/kg (range, 172 to 205 ml/kg). Median terminal half-life of eltenac was 2.40 hours (range, 2.11 to 3.25 hours). Protein binding of eltenac, determined by ultrafiltration, was > 99% at a total plasma concentration of 36 μg/ml.

Conclusion

Pharmacokinetic variables determined for each horse were not different between days 0 and 4.

Clinical Relevance

Under conditions of this study, there was no clinically relevant accumulation of eltenac in equine plasma or alteration of pharmacokinetic variables after multiple IV dosing of 0.5 mg/kg of eltenac. (Am J Vet Res 1998;59:1447–1450)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine the effects of acute exercise on hepatic blood flow by studying hepatic clearance of bromsulphalein for several submaximal exercise intensities.

Animals

8 adult Standardbred mares.

Procedure

Horses were subjected to 4 submaximal exercise intensities (resting and 40, 60, and 80% maximal oxygen consumption). After horses had been running at the required treadmill speed for 1 minute, bromsulphalein (BSP; 5 mg/kg of body weight, IV) was administered during a 45- to 60-second period, and horses continued at the desired speed for an additional 15 minutes. Blood samples were collected at 2-minute intervals for 30 minutes, and plasma concentration of BSP was determined by spectrophotometry. Estimates of pharmacokinetic variables were compared among the 4 exercise intensities, using a Friedman repeated-measures analysis on ranks and linear regression.

Results

Median values for clearance of BSP from blood and plasma decreased significantly with exercise and was linearly related to exercise intensity. Exercise-induced differences were not detected in the volume of distribution of BSP. Elimination half-life of BSP increased significantly with increasing exercise intensity and was linearly related to exercise intensity.

Conclusions

Acute submaximal exercise has a dramatic effect on clearance of BSP in horses. Presumably, exercise-induced decreases in splanchnic blood flow limit blood flow to the liver, decreasing hepatic clearance of BSP and leading to persistence of plasma concentrations of BSP.

Clinical Implications

Drugs that are efficiently extracted by the liver may have decreased hepatic clearance when horses exercise at submaximal intensities. (Am J Vet Res 1998;59:1481–1487)

Free access
in American Journal of Veterinary Research

SUMMARY

The effect of premedication with phenylbutazone on systemic hemodynamic and diuretic effects of furosemide was examined in 6 healthy, conscious, mares. Mares were instrumented for measurement of systemic hemodynamics, including cardiac output and pulmonary arterial, systemic arterial, and intracardiac pressures, and urine flow. Each of 3 treatments was administered in a randomized, blinded study; furosemide (1 mg/kg of body weight, iv) only, phenylbutazone (8.8 mg/kg, po, at 24 hours and 4.4 mg/kg, iv, 30 minutes before furosemide) and furosemide, or 0.9% NaCl. Phenylbutazone administration significantly attenuated, but did not abolish, the diuretic effect of furosemide. Phenylbutazone completely inhibited the immediate effect of furosemide on cardiac output, stroke volume, total peripheral resistance, and right ventricular peak pressure. Premedication with phenylbutazone did not inhibit equally the diuretic and hemodynamic effects of furosemide, indicating that some of furosemide's hemodynamic effects are mediated by an extrarenal activity of furosemide.

Free access
in American Journal of Veterinary Research
in American Journal of Veterinary Research

Abstract

Objective

To determine pharmacokinetic variables that describe disposition of ketoprofen after its IV administration to foals < 24 hours old.

Animals

6 healthy foals (1 male and 5 females); mean age, 12.5 (range, 8.5 to 17) hours at time of dose administration.

Procedure

Ketoprofen was administered IV to foals at a dosage of 2.2 mg/kg of body weight. Ketoprofen concentration in plasma samples was analyzed, using high-performance liquid chromatography. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined times during a 48-hour period. Samples were centrifuged, and plasma was frozen at −70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by use of Akaike's information criterion analysis.

Results

Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance (normalized for body weight) was significantly lower than that determined for adult horses. Volume of distribution (normalized for body weight) was larger than that determined for adult horses. Mean (harmonic) plasma half-life for healthy foals < 24 hours old was 4.3 hours.

Clinical Relevance

Although additional factors, such as dehydration or sepsis, must be considered on a case-by-case basis, the dose of ketoprofen administered to foals < 24 hours old should be different from the dose administered to adult horses. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to produce comparable therapeutic concentrations; longer dose intervals, based on clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1998;59:290–292)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To measure renal clearance of antipyrine and urinary excretion of antipyrine (AP) metabolites in horses by use of validated high-performance liquid chromatography (HPLC) methods.

Animals

8 Standardbred mares.

Procedure

HPLC methods for measurement of AP in equine plasma and AP and its metabolites in equine urine were validated. Antipyrine (20 mg/kg of body weight) was administered IV, and blood samples and urine specimens were collected over 24 hours.

Results

Median plasma clearance of AP in horses was 6.2 ml/min/kg, of which < 2% could be attributed to renal clearance. Urinary excretion of AP and its metabolites over 24 hours accounted for < 22% of the AP dose administered. The major metabolite of AP in urine was 4-hydroxyantipyrine.

Conclusions and Clinical Relevance

Use of the proven validated methods for measuring AP and its metabolites indicated that AP has minimal renal clearance in horses, suggesting that plasma clearance of AP reflects hepatic clearance. Combined with AP metabolite data, the pharmacokinetics of AP may be useful for assessment of hepatic cytochrome P450 activity in horses. (Am J Vet Res 1998;59:280–285)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine anterior chamber ocular measurements of adult porcine globes without histologic fixation by use of ultrasound biomicroscopy scanning.

Sample Population

25 porcine globes obtained at an abattoir.

Procedure

Globes were packed on ice for transport. In the laboratory, globes were trimmed, rinsed with antibiotic solution, secured on a single gauze-fold in a latex holder, then were ultrasonogrammed unreformed. Ultrasound biomicroscopy scanning was done, using a 50-MHz transducer, 17-mm cup, and 2% methyl cellulose.

Results

Average young adult pig external ocular measurements were: nasal-temporal corneal diameter, 16.61mm; superior-inferior corneal diameter, 14.00 mm; nasal-temporal globe diameter, 25.48 mm; superior-inferior globe diameter, 24.48 mm; and axial length 21.64 mm. Ultrasound biomicroscopy anterior chamber measurements were: iris sulcus, 30.45°; ciliary sulcus, 18.89°; central corneal thickness, 0.98 mm; corneal thickness at limbus, 1.19 mm; central iris thickness, 0.58 mm; iris tip to ciliary apex, 1.73 mm; iris tip to iris sulcus origin, 3.83 mm; iris tip to ciliary sulcus origin, 2.98 mm; anterior chamber depth from iris tip to cornea, 2.21 mm; central anterior chamber depth, 2.47 mm; ciliary process mid-thickness, 0.65 mm; ciliary process apex to origin of iris sulcus, 2.32 mm; ciliary process apex to origin of ciliary sulcus, 1.34 mm; zonular bundle diameter, 0.10 mm; and interzonular bundle space, 0.11 mm.

Conclusions

Anatomic anterior chamber measurements and relations in porcine globes can be used to describe trauma, confirm existence of lesions, and help explain theory.

Clinical Relevance

Ultrasound biomicroscopy is a clinical decision aid facilitating noninvasive anatomic or pathologic description without histologic fixation. (Am J Vet Res 1997;58:942–948)

Free access
in American Journal of Veterinary Research

Abstract

Objective

To determine pharmacokinetic variables that describe the disposition of flunixin after IV administration of flunixin meglumine to foals < 24 hours old.

Animals

6 healthy foals, 2 males and 4 females (mean age, 11.6 hours; range, 6 to 22.5 hours).

Procedure

Flunixin (as flunixin meglumine) was administered to foals at a dosage of 1.1 mg/kg of body weight. Flunixin concentration in plasma samples was analyzed, using gas chromatography/mass spectroscopy. Concentration versus time profiles were analyzed according to standard pharmacokinetic techniques. Blood samples were obtained from foals by jugular venipuncture at defined intervals over a 48-hour period. Samples were centrifuged, and plasma was frozen at −70 C until analyzed. One-, two-, and three-compartment analyses were conducted. The most appropriate model was determined by Akaike's information criterion analysis.

Results

Plasma concentration versus time profiles were best described, using a two-compartment open model. Clearance was significantly lower than that determined for older foals and adult horses. Volume of distribution was larger than that determined for adults. Mean plasma halflife for healthy foals < 24 hours old was 8.5 hours.

Conclusions and Clinical Relevance

Although additional factors (eg, dehydration or sepsis) must be considered on a case-by-case basis, flunixin meglumine should be administered differently to foals < 24 hours old, compared with adults. Under similar clinical circumstances, doses in foals should be increased by as much as 1.5 times to induce comparable therapeutic concentrations; longer dose intervals, on the basis of clinical response, would be necessary to avoid drug toxicity. (Am J Vet Res 1996;57:1759–1761)

Free access
in American Journal of Veterinary Research