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OBJECTIVE To determine pharmacokinetics after IM and oral administration of a single dose of meloxicam to American flamingos (Phoenicopertus ruber).

ANIMALS 14 adult flamingos.

PROCEDURES Flamingos were allocated to 2 groups. Each group received a dose of meloxicam (1 mg/kg) by the IM or oral route. After a 4-week washout period, groups received meloxicam via the other route of administration. Plasma meloxicam concentrations were measured with high-performance liquid chromatography. Data for each bird were analyzed. Estimated values of selected pharmacokinetic parameters were compared by use of a linear mixed-effects ANOVA. Pooled concentration-time profiles for each route of administration were analyzed to examine the influence of body weight on pharmacokinetics.

RESULTS Mean ± SD maximum plasma concentration was 1.00 ± 0.88 μg/mL after oral administration. This was approximately 15% of the mean maximum plasma concentration of 5.50 ± 2.86 μg/mL after IM administration. Mean time to maximum plasma concentration was 1.33 ± 1.32 hours after oral administration and 0.28 ± 0.17 hours after IM administration. Mean half-life of the terminal phase after oral administration (3.83 ± 2.64 hours) was approximately twice that after IM administration (1.83 ± 1.22 hours).

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the extent and rate of meloxicam absorption were less after oral administration than after IM administration. Intramuscular administration resulted in a short period during which mean plasma concentrations met or exceeded reported efficacious analgesic concentrations in other species, whereas oral administration did not. These results suggested that higher doses may be required for oral administration.

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in American Journal of Veterinary Research



To develop and validate a population pharmacokinetic model for gentamicin in horses, using retrospective clinical data.


62 horses that had been treated IV with multiple doses of gentamicin at our veterinary teaching hospital between 1987 and 1996.


46 horses were assigned to the study group, and 16 to the validation group. Detailed history of dosage, sample collection times, and selected pathophysiologic variables were recorded for each patient. Samples were analyzed by use of a fluorescence polarization immunoassay method. Pharm-acostatistical analysis was conducted, using computer software. The predictive model correlates pharmacokinetic parameters to concomitant pathophysiologic variables and estimates the inter- and intraindividual variability in disposition.


A two-compartment model best described the data. Clearance (Cl) was linearly correlated to body weight and serum creatinine concentration. Volume of the central compartment (Vdc) was linearly related to body weight. Interindividual coefficients of variability for Cl and Vdc were 24 and 16%, respectively. The residual variability (intraindividual) was 13%; mean prediction error percent (bias) was 2%; and mean absolute prediction error percent (precision) was 29%.


Population pharmacokinetic analysis allows study of the basic features of gentamicin disposition in horses with sparse data per individual. A considerable proportion of the pharmacokinetic variability of gentamicin in our study population was explained by differences in body weight and serum creatinine concentration.

Clinical Relevance

Population pharmacokinetics can be used to design first-dosage regimens according to the clinical characteristics of individual animals. Population pharmacokinetic models could also be included in Bayesian forecasting strategies to improve plasma concentration predictions in individual patients. (Am J Vet Res 1998;59:1589-1598)

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


Objective—To evaluate effects of small intestinal submucosa (SIS) on elution properties of plaster of Paris (POP).

Sample Population—27 POP cylinders, 27 POP spheres, and 9 polymethylmethacrylate (PMMA) spheres.

Procedures—Pellets were loaded with gentamicin (50 mg/g) and divided into 7 groups of 9 beads each: PMMA spheres; POP cylinders coated with 0, 4, or 8 layers of SIS; and POP spheres coated with 0, 4, or 8 layers of SIS. Gentamicin concentration was measured 6, 12, 18, 24, 32, 40, and 48 hours and 3, 4, 5, 7, 14, 21, 28, 35, and 42 days after wrapping. Porosity was evaluated via scanning electron microscopy. Curvature factor of elution curves, total amount of drug released (TDR), time required to reach 50% of total release (TDRt50), and number of days with concentrations ≥ 1 μg/mL were compared among groups.

Results—SIS decreased the curvature factor and increased the TDRt50 and TDR of POP spheres and cylinders. Curvature factor of the PMMA-release curve remained lower than that for any POP group, but all POP groups wrapped in SIS released more gentamicin than PMMA spheres. Gentamicin concentrations remained ≥ 1 μg/mL in SIS-wrapped POP and PMMA groups throughout the study. Wrapping POP in SIS minimized the increase in porosity of pellets.

Conclusions and Clinical Relevance—Wrapping POP with SIS slows the release and increases the amount of gentamicin leaching from spheres and cylinders. All groups wrapped in SIS maintained antimicrobial concentrations greater than the minimum inhibitory concentration of most pathogens.

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in American Journal of Veterinary Research


Objective—To evaluate the pharmacokinetics of diazepam administered per rectum via compounded (ie, not commercially available) suppositories and determine whether a dose of 2 mg/kg in this formulation would result in plasma concentrations shown to be effective for control of status epilepticus or cluster seizures (ie, 150 to 300 ng/mL) in dogs within a clinically useful interval (10 to 15 minutes).

Animals—6 healthy mixed-breed dogs.

Procedures—Dogs were randomly assigned to 2 groups of 3 dogs each in a crossover-design study. Diazepam (2 mg/kg) was administered IV or via suppository per rectum, and blood samples were collected at predetermined time points. Following a 6- or 7-day washout period, each group received the alternate treatment. Plasma concentrations of diazepam and nordiazepam were analyzed via reversed phase high-performance liquid chromatography.

Results—Plasma concentrations of diazepam and nordiazepam exceeded the targeted range ≤ 3 minutes after IV administration in all dogs. After suppository administration, targeted concentrations of diazepam were not detected in any dogs, and targeted concentrations of nordiazepam were detected after 90 minutes (n = 2 dogs) or 120 minutes (3) or were not achieved (1).

Conclusions and Clinical Relevance—On the basis of these results, administration of 2 mg of diazepam/kg via the compounded suppositories used in the present study cannot be recommended for emergency treatment of seizures in dogs.

Full access
in American Journal of Veterinary Research


Objective—To evaluate sedative, antinociceptive, and physiologic effects of acepromazine and butorphanol during tiletamine-zolazepam (TZ) anesthesia in llamas.

Animals—5 young adult llamas.

Procedures—Llamas received each of 5 treatments IM (1-week intervals): A (acepromazine, 0.05 mg/kg), B1 (butorphanol, 0.1 mg/kg), AB (acepromazine, 0.05 mg/kg, and butorphanol, 0.1 mg/kg), B2 (butorphanol, 0.2 mg/kg), or C (saline [0.9% NaCl] solution). Sedation was evaluated during a 30-minute period prior to anesthesia with TZ (2 mg/kg, IM). Anesthesia and recovery characteristics and selected cardiorespiratory variables were recorded at intervals. Antinociception was assessed via a toe-clamp technique.

Results—Sedation was not evident following any treatment. Times to sternal and lateral recumbency did not differ among treatments. Duration of lateral recumbency was significantly longer for treatment AB than for treatment C. Duration of antinociception was significantly longer for treatments A and AB, compared with treatment C, and longer for treatment AB, compared with treatment B2. Treatment B1 resulted in a significant decrease in respiratory rate, compared with treatment C. Compared with treatment C, diastolic and mean blood pressures were lower after treatment A. Heart rate was increased with treatment A, compared with treatment B1 or treatment C. Although severe hypoxemia developed in llamas anesthetized with TZ alone and with each treatment-TZ combination, hemoglobin saturation remained high and the hypoxemia was not considered clinically important.

Conclusions and Clinical Relevance—Sedation or changes in heart and respiratory rates were not detected with any treatment before administration of TZ. Acepromazine alone and acepromazine with butorphanol (0.1 mg/kg) prolonged the duration of antinociception in TZ-treated llamas.

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in American Journal of Veterinary Research


Objective—To determine the pharmacokinetics after oral administration of a single dose of ponazuril to healthy llamas.

Animals—6 healthy adult llamas.

Procedures—Ponazuril (20 mg/kg) was administered once orally to 6 llamas (day 0). Blood samples were obtained on days 0, 0.5, 1, 2, 3, 4, 5, 6, 7, 9, 11, 14, 21, 28, 35, 42, and 49. Serum ponazuril concentrations were determined by use of a validated reverse-phase high-performance liquid chromatography assay with UV absorbance detection. Pharmacokinetic parameters were derived by use of a standard noncompartmental pharmacokinetic analysis.

Results—Mean ± SD area under the serum concentration–time curve was 7,516 ± 2,750 h•mg/L, maximum serum ponazuril concentration was 23.6 ± 6.0 mg/L, and the elimination half-life was 135.5 ± 16.7 hours. Serum concentration of ponazuril peaked at 84 hours (range, 48 to 120 hours) after administration and gradually decreased but remained detectable for up to 35 days after administration. No adverse effects were observed during the study period.

Conclusions and Clinical Relevance—The rate and extent of absorption following oral administration of a single dose of ponazuril were sufficient to result in potentially effective concentrations, and the drug was tolerated well by llamas. At this dose, ponazuril resulted in serum concentrations that were high enough to be effective against various Apicomplexans on the basis of data for other species. The effective ponazuril concentration that will induce 50% inhibition of parasite growth for Eimeria macusaniensis in camelids is currently unknown.

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in American Journal of Veterinary Research


Objective—To determine the hemodynamic consequences of the coadministration of a continuous rate infusion (CRI) of medetomidine with a fentanyl bolus in dogs.

Animals—12 healthy sexually intact male dogs weighing 30.3 ± 4.2 kg (mean ± SD).

Procedure—Dogs received either fentanyl alone (15.0 µg/kg, IV bolus) or the same dose of fentanyl during an 11-hour CRI of medetomidine (1.5 µg/kg/h, IV). Prior to drug administration, dogs were instrumented for measurement of cardiac output, left atrial pressure, and systemic arterial blood pressures. Additionally, blood samples were collected from the pulmonary artery and left atrium for blood gas analysis.

Results—Medetomidine infusion reduced the cardiac index, heart rate, and O2 delivery while increasing left atrial pressure. Subsequent fentanyl administration further decreased the cardiac index. The PaO2 was not significantly different between the 2 treatment groups; however, fentanyl transiently decreased PaO2 from baseline values in dogs receiving a CRI of medetomidine.

Conclusions and Clinical Relevance—Because of the prolonged hemodynamic changes associated with the CRI of medetomidine, its safety should be further evaluated before being clinically implemented in dogs. (Am J Vet Res 2005;66:1222–1226)

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in American Journal of Veterinary Research


OBJECTIVE To determine the pharmacokinetics of orally administered rapamycin in healthy dogs.

ANIMALS 5 healthy purpose-bred hounds.

PROCEDURES The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography–tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses.

RESULTS Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

Full access
in American Journal of Veterinary Research