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- Author or Editor: Mark Papich x
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Abstract
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.
Design—Evaluation study.
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.
Abstract
Objective—To determine the pharmacokinetics of enrofloxacin after oral administration to captive elephants.
Animals—6 clinically normal adult Asian elephants (Elephas maximus).
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 chromatography.
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 Res 2005;66:1948–1953)
Abstract
Objective—To evaluate the bioavailability and pharmacokinetic characteristics of 2 commercially available extended-release theophylline formulations in dogs.
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 immunoassay.
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)
Abstract
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.
Abstract
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.
Design—Original study.
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).
Abstract
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.
Abstract
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)
Abstract
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 old).
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)
Abstract
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) were assessed.
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)
Abstract
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.
