Case Description—A 24-year-old 732-kg (1,610-lb) pregnant Belgian draft horse mare developed neuropathy and signs of intractable pain following colic surgery.
Clinical Findings—Following recovery from colic surgery to treat compression of the small and large intestines because of a large fetus, the mare was noticed to have signs of femoral neuropathy involving the left hind limb. Within 36 hours after recovery, the mare developed signs of severe pain that were unresponsive to conventional treatment. No gastrointestinal tract or muscular abnormalities were found, and the discomfort was attributed to neuropathic pain.
Treatment and Outcome—The mare was treated with gabapentin (2.5 mg/kg [1.1 mg/lb], PO, q 12 h). Shortly after this treatment was initiated, the mare appeared comfortable and no longer had signs of pain. Treatment was continued for 6 days, during which the dosage was progressively decreased, and the mare was discharged. The mare subsequently delivered a healthy foal.
Clinical Relevance—Gabapentin appeared to be a safe, effective, and economical treatment for neuropathic pain in this horse.
Objective—To determine whether ultrasonography
would be useful in the diagnosis of right dorsal colitis
Animals—5 horses with right dorsal colitis and 15
healthy adult horses.
Procedure—Mural thickness and appearance of the
right dorsal colon were determined from ultrasonographic
images obtained at right intercostal spaces
10, 11, 12, 13, and 14.
Results—The right dorsal colon could be imaged
most consistently at the right 11th, 12th, and 13th
intercostal spaces, below the margin of the lung and
axial to the liver. Mural thickness measured from
ultrasonographic images was significantly greater in
horses with right dorsal colitis than in healthy horses.
The right dorsal colon in affected horses had a prominent
hypoechoic layer associated with submucosal
edema and inflammatory infiltrates. Successful treatment
of 1 horse with right dorsal colitis was associated
with a decrease in mural thickness coincident with
an increase in serum albumin and total protein concentrations
and weight gain. A decrease in mural
thickness was also observed in a second horse treated
for right dorsal colitis that was not associated with
healing of the right dorsal colon or an increase in
serum albumin concentration but rather thinning of a
segment of the right dorsal colon that eventually ruptured.
Conclusions and Clinical Relevance—Results suggest
that ultrasonographic measurement of mural
thickness and evaluation of the appearance of the
right dorsal colon may be useful in the diagnosis of
right dorsal colitis in horses. (J Am Vet Med Assoc 2003;222:1248–1251)
Objective—To determine the effect of protein binding on the pharmacokinetics and distribution from plasma to interstitial fluid (ISF) of cephalexin and cefpodoxime proxetil in dogs.
Animals—6 healthy dogs.
Procedures—In a crossover study design, 25 mg of cephalexin/kg or 9.6 mg of cefpodoxime/kg was administered orally. Blood samples were collected before (time 0) and 0.33, 0.66, 1, 2, 3, 4, 6, 8, 10, 12, 16, and 24 hours after treatment. An ultrafiltration device was used in vivo to collect ISF at 0, 2, 4, 6, 8, 10, 12, 16, and 24 hours. Plasma and ISF concentrations were analyzed with high-pressure liquid chromatography. Plasma protein binding was measured by use of a microcentrifugation technique.
Results—Mean plasma protein binding for cefpodoxime and cephalexin was 82.6% and 20.8%, respectively. Mean ± SD values for cephalexin in plasma were determined for peak plasma concentration (Cmax, 31.5 ± 11.5 μg/mL), area under the time-concentration curve (AUC, 155.6 ± 29.5 μg•h/mL), and terminal half-life (T½, 4.7 ± 1.2 hours); corresponding values in ISF were 16.3 ± 5.8 μg/mL, 878 ± 21.0 μg•h/mL, and 3.2 ± 0.6 hours, respectively. Mean ± SD values for cefpodoxime in plasma were 33.0 ± 6.9 μg/mL (Cmax), 282.8 ± 44.0 μg•h/mL (AUC), and 5.7 ± 0.9 hours (T1/2); corresponding values in ISF were 4.3 ± 2.0 μg/mL, 575 ± 174 μg•h/mL, and 10.4 ± 3.3 hours, respectively.
Conclusions and Clinical Relevance—Tissue concentration of protein-unbound cefpodoxime was similar to that of the protein-unbound plasma concentration. Cefpodoxime remained in tissues longer than did cephalexin.
Objective—To determine the effects of temperature and light over a 35-day period on stability of pergolide mesylate after compounding in an aqueous vehicle.
Procedures—Pergolide was compounded into a formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at −20°, 8°, 25°, or 37°C without exposure to light or at 25°C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 days of storage.
Results—Mean ± SD concentration of pergolide in the formulation immediately after compounding was 1.05 ± 0.086 mg/mL. Samples exposed to light while stored at 25°C had undergone excessive degradation by day 14, samples stored at 37°C had undergone excessive degradation by day 21, and samples stored at 25°C without exposure to light had undergone excessive degradation by day 35. The decrease in expected concentration corresponded with the appearance of degradation peaks in chromatograms and with a change in color of the formulation.
Conclusions and Clinical Relevance—Results indicated that pergolide mesylate was unstable after compounding in an aqueous vehicle and that storage conditions had an effect on stability of the compounded formulation. Compounded pergolide formulations in aqueous vehicles should be stored in a dark container, protected from light, and refrigerated and should not be used > 30 days after produced. Formulations that have undergone a color change should be considered unstable and discarded.
Objective—To determine pharmacokinetics, safety, and penetration into interstitial fluid (ISF), polymorphonuclear leukocytes (PMNLs), and aqueous humor of doxycycline after oral administration of single and multiple doses in horses.
Animals—6 adult horses.
Procedure—The effect of feeding on drug absorption was determined. Plasma samples were obtained after administration of single or multiple doses of doxycycline (20 mg/kg) via nasogastric tube. Additionally, ISF, PMNLs, and aqueous humor samples were obtained after the final administration. Horses were monitored for adverse reactions.
Results—Feeding decreased drug absorption. After multiple doses, mean ± SD time to maximum concentration was 1.63 ± 1.36 hours, maximum concentration was 1.74 ± 0.3 μg/mL, and elimination half-life was 12.07 ± 3.17 hours. Plasma protein binding was 81.76 ± 2.43%. The ISF concentrations correlated with the calculated percentage of non-protein-bound drug. Maximum concentration was 17.27 ± 8.98 times as great in PMNLs, compared with plasma. Drug was detected in aqueous humor at 7.5% to 10% of plasma concentrations. One horse developed signs of acute colitis and required euthanasia.
Conclusions and Clinical Relevance—Results suggest that doxycycline administered at a dosage of 20 mg/kg, PO, every 24 hours will result in drug concentrations adequate for killing intracellular bacteria and bacteria with minimum inhibitory concentration ≤ 0.25 μg/mL. For bacteria with minimum inhibitory concentration of 0.5 to 1.0 μg/mL, a dosage of 20 mg/kg, PO, every 12 hours may be required; extreme caution should be exercised with the higher dosage until more safety data are available.
Objective—To characterize pharmacokinetics of voriconazole in horses after oral and IV administration and determine the in vitro physicochemical characteristics of the drug that may affect oral absorption and tissue distribution.
Animals—6 adult horses.
Procedures—Horses were administered voriconazole (1 mg/kg, IV, or 4 mg/kg, PO), and plasma concentrations were measured by use of high-performance liquid chromatography. In vitro plasma protein binding and the octanol:water partition coefficient were also assessed.
Results—Voriconazole was adequately absorbed after oral administration in horses, with a systemic bioavailability of 135.75 ± 18.41%. The elimination half-life after a single orally administered dose was 13.11 ± 2.85 hours, and the maximum plasma concentration was 2.43 ± 0.4 μg/mL. Plasma protein binding was 31.68%, and the octanol:water partition coefficient was 64.69. No adverse reactions were detected during the study.
Conclusions and Clinical Relevance—Voriconazole has excellent absorption after oral administration and a long half-life in horses. On the basis of the results of this study, it was concluded that administration of voriconazole at a dosage of 4 mg/kg, PO, every 24 hours will attain plasma concentrations adequate for treatment of horses with fungal infections for which the fungi have a minimum inhibitory concentration ≤ 1 μg/mL. Because of the possible nonlinearity of this drug as well as the potential for accumulation, chronic dosing studies and clinical trials are needed to determine the appropriate dosing regimen for voriconazole in horses.
Objective—To determine the pharmacokinetics of
itraconazole after IV or oral administration of a solution
or capsules to horses and to examine disposition
of itraconazole in the interstitial fluid (ISF), aqueous
humor, and polymorphonuclear leukocytes after oral
administration of the solution.
Animals—6 healthy horses.
Procedure—Horses were administered itraconazole
solution (5 mg/kg) by nasogastric tube, and samples of
plasma, ISF, aqueous humor, and leukocytes were
obtained. Horses were then administered itraconazole
capsules (5 mg/kg), and plasma was obtained. Three
horses were administered itraconazole (1.5 mg/kg, IV),
and plasma samples were obtained. All samples were
analyzed by use of high-performance liquid chromatography.
Plasma protein binding was determined. Data
were analyzed by compartmental and noncompartmental
Results—Itraconazole reached higher mean ± SD
plasma concentrations after administration of the
solution (0.41 ± 0.13 µg/mL) versus the capsules
(0.15 ± 0.12 µg/mL). Bioavailability after administration
of capsules relative to solution was 33.83 ±
33.08%. Similar to other species, itraconazole has a
high volume of distribution (6.3 ± 0.94 L/kg) and a
long half-life (11.3 ± 2.84 hours). Itraconazole was not
detected in the ISF, aqueous humor, or leukocytes.
Plasma protein binding was 98.81 ± 0.17%.
Conclusions and Clinical Relevance—Itraconazole
administered orally as a solution had higher, more
consistent absorption than orally administered capsules
and attained plasma concentrations that are
inhibitory against fungi that infect horses.
Administration of itraconazole solution (5 mg/kg, PO,
q 24 h) is suggested for use in clinical trials to test the
efficacy of itraconazole in horses. (Am J Vet Res
Objective—To identify clinical signs, underlying cardiac
conditions, echocardiographic findings, and prognosis
for horses with congestive heart failure.
Procedure—Signalment; history; clinical signs; clinicopathologic,
echocardiographic, and radiographic
findings; treatment; and outcome were determined
by reviewing medical records.
Results—All 14 horses were examined because of a
heart murmur; tachycardia was identified in all 14.
Twelve horses had echocardiographic evidence of
enlargement of 1 or more chambers of the heart.
Other common clinical findings included jugular distention
or pulsation, crackles, cough, tachypnea, and
ventral edema. Nine horses had signs consistent with
heart failure for > 6 days. Underlying causes for heart
failure included congenital defects, traumatic vascular
rupture, pericarditis, pulmonary hypertension secondary
to heaves, and valvular dysplasia. Seven horses
were euthanatized after diagnosis of heart failure;
5 were discharged but were euthanatized or died of
complications of heart disease within 1 year after discharge.
The remaining 2 horses were discharged but
lost to follow-up.
Conclusions and Clinical Relevance—Results suggest
that congestive heart failure is rare in horses. A loud
heart murmur accompanied by either jugular distention
or pulsation, tachycardia, respiratory abnormalities
(crackles, cough, tachypnea), and ventral edema were
the most common clinical signs. Echocardiography was
useful in determining the underlying cause in affected
horses. The long-term prognosis for horses with congestive
heart failure was grave. (J Am Vet Med Assoc
Objective—To determine elimination kinetics of tilmicosin in milk following intramammary administration in lactating dairy cattle.
Design—Prospective pharmacokinetic study.
Animals—6 lactating dairy cows.
Procedures—Following collection of baseline milk samples, 1,200 mg (4 mL) of tilmicosin was infused into the left front and right rear mammary glands of each cow. Approximately 12 hours later, an additional 1,200 mg of tilmicosin was infused into the left front and right rear glands after milking. Milk samples were then collected from each gland at milking time for 40 days. Concentration of tilmicosin was determined by means of ultraperformance liquid chromatography–mass spectrometry, and a milk withdrawal interval for tilmicosin was calculated on the basis of the tolerance limit method.
Results—Although there was considerable variation between glands, concentration of tilmicosin was high in milk from treated glands and had a long half-life in treated and untreated glands. Tilmicosin was detected in all treated glands for the entire 40-day study period and was detected in untreated glands for approximately 30 to 35 days.
Conclusions and Clinical Relevance—Findings indicated that tilmicosin should not be administered by the intramammary route in lactating dairy cows. Milk from all glands of any cows accidentally treated should be discarded for a minimum of 82 days following intramammary administration.
Objective—To determine the pharmacokinetics and safety of orally administered voriconazole in African grey parrots.
Animals—20 clinically normal Timneh African grey parrots (Psittacus erithacus timneh).
Procedures—In single-dose trials, 12 parrots were each administered 6, 12, and 18 mg of voriconazole/kg orally and plasma concentrations of voriconazole were determined via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) was administered orally to 6 birds every 12 hours for 9 days; a control group (2 birds) received tap water. Treatment effects were assessed via observation, clinicopathologic analyses (3 assessments), and measurement of trough plasma voriconazole concentrations (2 assessments).
Results—Voriconazole's elimination half-life was short (1.1 to 1.6 hours). Higher doses resulted in disproportional increases in the maximum plasma voriconazole concentration and area under the curve. Trough plasma voriconazole concentrations achieved in the multiple-dose trial were lower than those achieved after administration of single doses. Polyuria (the only adverse treatment effect) developed in treated and control birds but was more severe in the treatment group.
Conclusions and Clinical Relevance—In African grey parrots, voriconazole has dose-dependent pharmacokinetics and may induce its own metabolism. Oral administration of 12 to 18 mg of voriconazole/kg twice daily is a rational starting dose for treatment of African grey parrots infected with Aspergillus or other fungal organisms that have a minimal inhibitory concentration for voriconazole ≤ 0.4 μg/mL. Higher doses may be needed to maintain plasma voriconazole concentrations during long-term treatment. Safety and efficacy of various voriconazole treatment regimens in this species require investigation.