Objective—To determine the concentration of doxycycline compounded from doxycycline hyclate tablets into liquid formulations for oral administration in veterinary species and stored for 28 days.
Sample—Doxycycline hyclate tablets (100 mg) crushed and mixed with a 50:50 mixture of syrup and suspension vehicles for oral administration to produce 3 batches each of 2 doxycycline formulations: 33.3 and 166.7 mg/mL.
Procedures—Formulations were stored, protected from light, at room temperature (22° to 26°C [71.6° to 78.8°F]) and at a controlled cold temperature (refrigerated 2° to 8°C [35.6° to 46.4°F]). Doxycycline was extracted from the formulations, and concentration was measured by high-pressure liquid chromatography on days 0 (date of preparation), 1, 4, 7, 14, 21, and 28. Concentrations were compared with those of a US Pharmacopeial Convention reference standard. Formulation quality at each point was also assessed through color change, formulation consistency, and suspension uniformity.
Results—On days 0, 1, 4, and 7, the concentration of each formulation was within 90% to 110% of the reference standard (range, 93% to 109%), which was deemed acceptable. However, doxycycline concentrations had decreased dramatically by day 14 and remained low for the duration of the study period. Doxycycline concentrations on days 14, 21, and 28 were all < 20% (range, 14% to 18%) of the reference standard, and the quality of the formulations decreased as well. No effect of storage temperatures on doxycycline concentration was identified.
Conclusions and Clinical Relevance—The concentration of doxycycline, compounded from commercial tablets in the vehicles evaluated to yield doses of 33.3 and 166.7 mg/mL, cannot be assured beyond 7 days.
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 the pharmacokinetics of
fluconazole in horses.
Animals—6 clinically normal adult horses.
Procedure—Fluconazole (10 mg/kg of body weight)
was administered intravenously or orally with 2
weeks between treatments. Plasma fluconazole concentrations
were determined prior to and 10, 20, 30,
40, and 60 minutes and 2, 4, 6, 8, 10, 12, 24, 36, 48,
60, and 72 hours after administration. A long-term oral
dosing regimen was designed in which all horses
received a loading dose of fluconazole (14 mg/kg) followed
by 5 mg/kg every 24 hours for 10 days.
Fluconazole concentrations were determined in aqueous
humor, plasma, CSF, synovial fluid, and urine after
administration of the final dose.
Results—Mean (± SD) apparent volume of distribution
of fluconazole at steady state was 1.21 ± 0.01
L/kg. Systemic availability and time to maximum plasma
concentration following oral administration were
101.24 ± 27.50% and 1.97 ± 1.68 hours, respectively.
Maximum plasma concentrations and terminal halflives
after IV and oral administration were similar.
Plasma, CSF, synovial fluid, aqueous humor, and urine
concentrations of fluconazole after long-term oral
administration of fluconazole were 30.50 ± 23.88,
14.99 ± 1.86, 14.19 ± 5.07, 11.39 ± 2.83, and 56.99 ±
32.87 µg/ml, respectively.
Conclusion and Clinical Relevance—Bioavailability
of fluconazole was high after oral administration to
horses. Long-term oral administration maintained plasma
and body fluid concentrations of fluconazole above
the mean inhibitory concentration (8.0 mg/ml) reported
for fungal pathogens in horses. Fluconazole may be
an appropriate agent for treatment of fungal infections
in horses. (Am J Vet Res 2001;62:1606–1611).
Objective—To determine the pharmacokinetics of
enrofloxacin after oral administration to captive elephants.
Animals—6 clinically normal adult Asian elephants
Procedure—Each elephant received a single dose of
enrofloxacin (2.5 mg/kg, PO). Three elephants
received their complete diet (pellets and grain) within
2 hours after enrofloxacin administration, whereas
the other 3 elephants received only hay within 6
hours after enrofloxacin administration. Serum concentrations
of enrofloxacin and ciprofloxacin were
measured by use of high-performance liquid
Results—Harmonic mean half-life after oral administration
was 18.4 hours for all elephants. Mean ± SD peak
serum concentration of enrofloxacin was 1.31 ±
0.40 µg/mL at 5.0 ± 4.2 hours after administration. Mean
area under the curve was 20.72 ± 4.25 (µg × h)/mL.
Conclusions and Clinical Relevance—Oral administration
of enrofloxacin to Asian elephants has a prolonged
elimination half-life, compared with the elimination
half-life for adult horses. In addition, potentially
therapeutic concentrations in elephants were
obtained when enrofloxacin was administered orally at
a dosage of 2.5 mg/kg. Analysis of these results suggests
that enrofloxacin administered with feed in the
manner described in this study could be a potentially
useful antimicrobial for use in treatment of captive
Asian elephants with infections attributable to organisms,
such as Bordetella spp, Escherichia coli,
Mycoplasma spp, Pasteurella spp, Haemophilus spp,
Salmonella spp, and Staphylococcus spp. (Am J Vet
Objective—To determine an infusion rate of butorphanol
tartrate in horses that would maintain therapeutic
plasma drug concentrations while minimizing
development of adverse behavioral and gastrointestinal
Animals—10 healthy adult horses.
Procedure—Plasma butorphanol concentrations
were determined by use of high-performance liquid
chromatography following administration of butorphanol
by single IV injection (0.1 to 0.13 mg/kg of
body weight) or continuous IV infusion (loading dose,
17.8 µg/kg; infusion dosage, 23.7 µg/kg/h for 24
hours). Pharmacokinetic variables were calculated,
and changes in physical examination data, gastrointestinal
tract transit time, and behavior were determined
Results—A single IV injection of butorphanol was
associated with adverse behavioral and gastrointestinal
tract effects including ataxia, decreased borborygmi,
and decreased defecation. Elimination half-life of
butorphanol was brief (44.37 minutes). Adverse gastrointestinal
tract effects were less apparent during
continuous 24-hour infusion of butorphanol at a
dosage that resulted in a mean plasma concentration
of 29 ng/ml, compared with effects after a single IV
injection. No adverse behavioral effects were
observed during or after continuous infusion.
Conclusions and Clinical Relevance—Continuous
IV infusion of butorphanol for 24 hours maintained
plasma butorphanol concentrations within a range
associated with analgesia. Adverse behavioral and
gastrointestinal tract effects were minimized during
infusion, compared with a single injection of butorphanol.
Continuous infusion of butorphanol may be a
useful treatment to induce analgesia in horses. (Am J
Vet Res 2001;62:183–189)
To describe patterns of antimicrobial prescriptions for sporadic urinary tract infections (UTIs) in dogs in the United States from 2010 through 2019, including times before and after publication of International Society for Companion Animal Infectious Disease (ISCAID) guidelines.
461,244 qualifying visits for sporadic UTIs.
Veterinary electronic medical records of a private corporation consisting of > 1,000 clinics across the United States were examined to identify canine visits for potential sporadic UTI between January 1, 2010, and December 31, 2019. Proportions of antimicrobial prescriptions were graphed by month and year to identify changes in prescription patterns over time. Interrupted time series analysis was performed for the aminopenicillins.
A total of 461,244 qualifying visits were examined, with 389,949 (85%) of these resulting in at least 1 antimicrobial prescription. Over the 10-year period, the proportion of visits resulting in no antimicrobial prescription increased (14% in 2010 to 19.7% in 2019). Proportions of prescriptions for amoxicillin (38% to 48%) and amoxicillin–clavulanic acid (2.5% to 10%) also increased. Log-linear regression supported that changes in proportions of amoxicillin and amoxicillin–clavulanic acid prescriptions occurred following the 2011 ISCAID guidelines publication, with the proportion of amoxicillin prescriptions increasing by 13% per year (95% CI, 12% to 14%; P < 0.01) and the proportion of amoxicillin–clavulanic acid prescriptions increasing by 0.5% per year (95% CI, 0.2% to 0.8%; P < 0.01). Use of fluoroquinolones and third-generation cephalosporins remained constant.
Results suggest that efforts to guide antimicrobial use in veterinary clinical practice are having positive effects in this private veterinary company, though continued efforts are warranted.
Objective—To evaluate the bioavailability and pharmacokinetic
characteristics of 2 commercially available
extended-release theophylline formulations in
Design—Randomized 3-way crossover study.
Animals—6 healthy adult dogs.
Procedure—A single dose of aminophylline (11 mg·kg–1
[5 mg·lb–1], IV, equivalent to 8.6 mg of theophylline/kg
[3.9 mg·lb–1]) or extended-release theophylline tablets
(mean dose, 15.5 mg·kg–1 [7.04 mg·lb–1], PO) or capsules
(mean dose, 15.45 mg·kg–1 [7.02 mg·lb–1], PO) was
administered to all dogs. Blood samples were obtained
at various times for 36 hours after dosing; plasma was
separated and immediately frozen. Plasma samples
were analyzed by use of fluorescence polarization
Results—Administration of theophylline IV best fit a
2-compartment model with rapid distribution followed
by slow elimination. Administration of extended-release
theophylline tablets and capsules best fit a 1-
compartment model with an absorption phase. Mean
values for plasma terminal half-life, volume of distribution,
and systemic clearance were 8.4 hours, 0.546
L·kg–1, and 0.780 mL·kg–1·min–1, respectively, after IV
administration of theophylline. Systemic availability
was > 80% for both oral formulations. Computer simulations
predicted that extended-release theophylline
tablets or capsules administered at a dosage of 10
mg·kg–1 (4.5 mg·lb–1), PO, every 12 hours would maintain
plasma concentrations within the desired therapeutic
range of 10 to 20 µg·mL–1.
Conclusions and Clinical Relevance—Results of
these single-dose studies indicated that administration
of the specific brand of extended-release theophylline
tablets or capsules used in this study at a
dosage of 10 mg·kg–1, PO, every 12 hours would
maintain plasma concentrations within the desired
therapeutic range (10 to 20 µg·mL–1) in healthy dogs.
(J Am Vet Med Assoc 2004;224:1113–1119)
Objective—To determine the pharmacokinetics of marbofloxacin after oral administration in juvenile harbor seals (Phoca vitulina) at a dose of 5 mg/kg (2.3 mg/lb) and to compare pharmacokinetic variables after pharmacokinetic analysis by naïve averaged, naïve pooled, and nonlinear mixed-effects modeling.
Animals—33 male and 22 female juvenile seals being treated for various conditions.
Procedures—Blood collection was limited to ≤ 3 samples/seal. Plasma marbofloxacin concentrations were measured via high-pressure liquid chromatography with UV detection.
Results—Mean ± SE dose of marbofloxacin administered was 5.3 ± 0.1 mg/kg (2.4 ± 0.05 mg/lb). The terminal half-life, volume of distribution (per bioavailability), and clearance (per bioavailability) were approximately 5 hours, approximately 1.4 L/kg, and approximately 3 mL/min/kg, respectively (values varied slightly with the method of calculation). Maximum plasma concentration and area under the plasma-time concentration curve were approximately 3 μg/mL and 30 h·μg/mL, respectively. Naïve averaged and naïve pooled analysis appeared to yield a better fit to the population, but nonlinear mixed-effects modeling yielded a better fit for individual seals.
Conclusions and Clinical Relevance—Values of pharmacokinetic variables were similar regardless of the analytic method used. Pharmacokinetic variability can be assessed with nonlinear mixed-effects modeling, but not with naïve averaged or naïve pooled analysis. Visual observation by experienced trainers revealed no adverse effects in treated seals. Plasma concentrations attained with a dosage of 5 mg/kg every 24 hours would be expected to be efficacious for treatment of infections caused by susceptible bacteria (excluding Pseudomonas aeruginosa).
Objective—To evaluate the pharmacokinetics of a brand of extended-release theophylline tablets and capsules in healthy cats.
Design—Randomized 3-way crossover study.
Animals—6 healthy cats.
Procedures—A single dose of aminophylline (10 mg/kg [4.5 mg/lb], IV), a 100-mg extended-release theophylline tablet, or a 125-mg extended-release theophylline capsule was administered to all cats. Plasma samples were collected via preplaced central catheters throughout a 36-hour period. Plasma samples were frozen until analyzed by use of a fluorescence polarization monoclonal immunoassay.
Results—All cats tolerated drug administration and plasma collection with no adverse effects. Peak concentrations were reached for both orally administered products between 8 and 12 hours after administration. Bioavailability was excellent. Plasma concentrations were within the human therapeutic concentration of 5 to 20 μg/mL.
Conclusions and Clinical Relevance—Daily administration of the brand of theophylline tablets and capsules used in this study at 15 mg/kg (6.8 mg/lb) and 19 mg/kg (8.6 mg/lb), respectively, maintained plasma concentrations within the desired therapeutic range in healthy cats.
Objective—To measure pharmacokinetics of levetiracetam (LEV) after single-dose oral administration in healthy dogs and determine whether pharmacokinetics changed after repeated oral dosing.
Animals—6 healthy adult dogs.
Procedures—Pharmacokinetics were calculated following administration of a single dose (mean, 21.7 mg/kg, PO; day 1) and after administration of the last dose following administration for 6 days (20.8 to 22.7 mg/kg, PO, q 8 h; days 2 to 7). Plasma LEV concentrations were determined by use of high-pressure liquid chromatography. Pharmacokinetic data were analyzed by use of a 1-compartment model with first-order absorption.
Results—Peak concentration occurred 0.6 hours after administration of the first dose, with an absorption half-life of 0.06 hours. Minimal accumulation occurred over the 7 days, with only a slight increase in total area under the concentration-versus-time curve from 268.52 ± 56.33 h·μg/mL (mean ± SD) to 289.31 ± 51.68 h·μg/mL after 7 days. Terminal half-life was 2.87 ± 0.21 hours after the first dose and 3.59 ± 0.82 hours after the last dose on day 7. Trough plasma concentrations were variable, depending on the time of day they were measured (morning trough concentration, 18.42 ± 5.16 μg/mL; midday trough concentration, 12.57 ± 4.34 μg/mL), suggesting a diurnal variation in drug excretion.
Conclusions and Clinical Relevance—Results indicated that the pharmacokinetics of LEV did not change appreciably after administration of multiple doses over 7 days. Administration of LEV at a dosage of 20 mg/kg, PO, every 8 hours to healthy dogs yielded plasma drug concentrations consistently within the therapeutic range established for LEV in humans.