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 compare absorption characteristics of orally administered compounded itraconazole capsules and suspension with those of reference (brand-name) formulations in healthy cats.
DESIGN Randomized crossover study.
ANIMALS 8 healthy adult cats.
PROCEDURES After 12 hours of food withholding, cats received 50 mg of itraconazole (reference capsule, reference solution, compounded capsule, and compounded suspension) in a randomized crossover design, with a 21-day washout period. Capsules were administered with a small meal. Blood samples were collected at predetermined intervals for high-pressure liquid chromatography analysis of plasma itraconazole concentrations. Area under the concentration-time curve, maximum concentration, and terminal half-life of itraconazole were determined and compared among formulations.
RESULTS 7 cats completed the study. Mean half-life of itraconazole in reference formulations was 18 to 26 hours. Absorption of the reference solution was 3 times that of the reference capsule. Compounded formulations were absorbed poorly and inconsistently. Complete pharmacokinetic results for the compounded capsule were obtained for only 3 of 6 cats and for the compounded suspension for only 1 of 5 cats, precluding bioequivalence analysis. Relative absorption of compounded formulations was only 2% to 8% of reference formulation values.
CONCLUSIONS AND CLINICAL RELEVANCE Compounded oral formulations of itraconazole should not be used for cats because of poor absorption. The differences in absorption between the 2 reference formulations suggested that doses required to meet human target serum concentrations in cats are markedly different (capsules, 12.5 mg/kg [5.7 mg/lb], q 24 h, with food; solution, 4 mg/kg [1.8 mg/lb], q 24 h, without food).
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 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)
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 define the pharmacokinetics of florfenicol in synovial fluid (SYNF) and serum from central venous (CV) and digital venous (DV) blood samples following regional IV perfusion (RIVP) of the distal portion of the hind limb in cows.
Animals—6 healthy adult cows.
Procedures—In each cow, IV catheters were placed in the dorsal common digital vein (DCDV) and the plantar vein of the lateral digit, and an indwelling catheter was placed in the metatarsophalangeal joint of the left hind limb. A pneumatic tourniquet was applied to the midmetatarsal region. Florfenicol (2.2 mg/kg) was administered into the DCDV. Samples of DV blood, SYNF, and CV (jugular) blood were collected after 0.25, 0.50, and 0.75 hours, and the tourniquet was removed; additional samples were collected at intervals for 24 hours after infusion. Florfenicol analysis was performed via high-performance liquid chromatography.
Results—In DV blood, CV blood, and SYNF, mean ± SD maximum florfenicol concentration was 714.79 ± 301.93 μg/mL, 5.90 ± 1.37 μg/mL, and 39.19 ± 29.42 μg/mL, respectively; area under the concentration versus time curve was 488.14 ± 272.53 h•μg•mL−1, 23.10 ± 6.91 h•μg•mL−1, and 113.82 ± 54.71 h•μg•mL−1, respectively; and half-life was 4.09 ± 1.93 hours, 4.77 ± 0.67 hours, and 3.81 ± 0.81 hours, respectively.
Conclusions and Clinical Relevance—Following RIVP, high florfenicol concentrations were achieved in DV blood and SYNF, whereas the CV blood concentration remained low. In cattle, RIVP of florfenicol may be useful in the treatment of infectious processes involving the distal portion of limbs.
Objective—To evaluate plasma glipizide concentration
and its relationship to plasma glucose and serum
insulin concentrations in healthy cats administered
glipizide orally or transdermally.
Animals—15 healthy adult laboratory-raised cats.
Procedure—Cats were randomly assigned to 2 treatment
groups (5 mg of glipizide, PO or transdermally)
and a control group. Blood samples were collected 0,
10, 20, 30, 45, 60, 90, and 120 minutes and 4, 6, 10,
14, 18, and 24 hours after administration to determine
concentrations of insulin, glucose, and glipizide.
Results—Glipizide was detected in all treated cats.
Mean ± SD transdermal absorption was 20 ± 14% of
oral absorption. Mean maximum glipizide concentration
was reached 5.0 ± 3.5 hours after oral and 16.0 ±
4.5 hours after transdermal administration. Elimination
half-life was variable (16.8 ± 12 hours orally
and 15.5 ± 15.3 hours transdermally). Plasma glucose
concentrations decreased in all treated cats, compared
with concentrations in control cats. Plasma glucose
concentrations were significantly lower 2 to 6
hours after oral administration, compared with after
transdermal application; concentrations were similar
between treatment groups and significantly lower
than for control cats 10 to 24 hours after treatment.
Conclusions and Clinical Relevance—Transdermal
absorption of glipizide was low and inconsistent, but
analysis of our results indicated that it did affect plasma
glucose concentrations. Transdermal administration
of glipizide is not equivalent to oral administration.
Formulation, absorption, and stability studies are
required before clinical analysis can be performed.
Transdermal administration of glipizide cannot be recommended
for clinical use at this time. (Am J Vet Res 2005;66:581–588)
Objective—To determine the pharmacokinetics of
enrofloxacin in neonatal kittens and compare the pharmacokinetics
of enrofloxacin in young and adult cats.
Animals—7 adult cats and 111 kittens (2 to 8 weeks
Procedure—A single dose of 5 mg of enrofloxacin/kg
was administered to adults (IV) and kittens (IV, SC, or
PO). Plasma concentrations of enrofloxacin and its
active metabolite, ciprofloxacin, were determined.
Results—The half-life of enrofloxacin administered IV
in 2-, 6-, and 8-week-old kittens was significantly
shorter and its elimination rate significantly greater
than that detected in adults. The apparent volumes of
distribution were lower at 2 to 4 weeks and greater at
6 to 8 weeks. This resulted in lower peak plasma concentration
(Cmax) at 6 to 8 weeks; however, initial plasma
concentration was within the therapeutic range
after IV administration at all ages. Compared with IV
administration, SC injection of enrofloxacin in 2-weekold
kittens resulted in similar Cmax, half-life, clearance,
and area under the curve values. Enrofloxacin administered
via SC injection was well absorbed in 6- and 8-
week-old kittens, but greater clearance and apparent
volume of distribution resulted in lower plasma concentrations.
Oral administration of enrofloxacin resulted
in poor bioavailability.
Conclusions and Clinical Relevance—In neonatal
kittens, IV and SC administration of enrofloxacin provided
an effective route of administration. Oral administration
of enrofloxacin in kittens did not result in
therapeutic drug concentrations. Doses may need to
be increased to achieve therapeutic drug concentrations
in 6- to 8-week-old kittens. ( Am J Vet Res 2004;65:350–356)
Objective—To determine whether infection with
Tritrichomonas foetus causes diarrhea in specific pathogen-free or Cryptosporidium coinfected cats.
Animals—4 cats with subclinical cryptosporidiosis
(group 1) and 4 specific-pathogen-free cats (group 2).
Procedure—Cats were infected orogastrically with an
axenic culture of T foetus isolated from a kitten with
diarrhea. Direct microscopy and protozoal culture of
feces, fecal character, serial colonic mucosal biopsy
specimens, and response to treatment with nitazoxanide
(NTZ; group 1) or prednisolone (groups 1 and 2)
Results—Infection with T foetus persisted in all cats
for the entire 203-day study and resulted in diarrhea
that resolved after 7 weeks. Group-1 cats had an earlier
onset, more severe diarrhea, and increased number
of trichomonads on direct fecal examination, compared
with group-2 cats. Use of NTZ eliminated shedding
of T foetus and Cryptosporidium oocysts, but
diarrhea consisting of trichomonad-containing feces
recurred when treatment was discontinued.
Prednisolone did not have an effect on infection with
T foetus but resulted in reappearance of
Cryptosporidium oocysts in the feces of 2 of 4 cats.
During necropsy, T foetus was isolated from contents
of the ileum, cecum, and colon. Tritrichomonas foetus
organisms and antigen were detected on surface
epithelia and within superficial detritus of the cecal
and colonic mucosa.
Conclusions and Clinical Relevance—After experimental
inoculation in cats, T foetus organisms colonize
the ileum, cecum, and colon, reside in close contact
with the epithelium, and are associated with transient
diarrhea that is exacerbated by coexisting cryptosporidiosis
but not treatment with prednisolone.
(Am J Vet Res 2001;62:1690–1697)
Objective—To determine the efficacy of tinidazole for treatment of cats with experimentally induced Tritrichomonas foetus infection.
Animals—8 specific-pathogen-free kittens.
Procedures—Tinidazole was tested for activity against a feline isolate of T foetus in vitro. Kittens were infected orogastrically with the same isolate and treated or not with tinidazole (30 mg/kg, PO, q 24 h for 14 days). Amoxicillin was administered 28 weeks after completion of tinidazole administration to induce diarrhea. Feces were repeatedly tested for T foetus by use of PCR assay and microbial culture for 33 weeks.
Results—Tinidazole killed T foetus at concentrations ≥ 10 μg/mL in vitro. In experimentally induced infection, tinidazole administered at 30 mg/kg decreased T foetus below the limit of molecular detection in 2 of 4 cats. Recrudescent shedding of T foetus, as elicited by amoxicillin-induced diarrhea, was diminished in cats that received prior treatment with tinidazole.
Conclusions and Clinical Relevance—Although tinidazole decreased the detection of T foetus and treated cats were resistant to later efforts to incite the infection, inability of tinidazole to eradicate infection in many cats poses a serious impediment to the drug’s effectiveness in practice.