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- Author or Editor: James W. Carpenter x
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Abstract
Objective—To determine pharmacokinetics, efficacy, and adverse effects of topically administered selamectin in flea-infested rabbits.
Animals—18 healthy 5-month-old New Zealand White rabbits.
Procedures—On day 0, rabbits (n = 6/group) received topically applied selamectin at doses of 10 or 20 mg/kg or received no treatment. Each rabbit was infested with 50 fleas (Ctenocephalides felis) on days −1, 7, and 14. Live and dead flea counts were performed on days 2, 9, and 16, and treatment efficacy was calculated. Blood samples were collected prior to drug administration and at 6 and 12 hours and 1, 2, 3, 5, 7, 10, 14, 21, and 28 days after treatment for determination of plasma selamectin concentrations via high-performance liquid chromatography with mass spectrometry. Pharmacokinetic parameters were determined.
Results—On day 2, efficacy of selamectin against flea populations of rabbits in the 10 and 20 mg/kg treatment groups was 91.3% and 97.1%, respectively, but by day 9, these values decreased to 37.7% and 74.2%, respectively. Mean terminal half-life and maximum plasma concentrations of selamectin were 0.93 days and 91.7 ng/mL, respectively, for rabbits in the 10 mg/kg group and 0.97 days and 304.2 ng/mL, respectively, for rabbits in the 20 mg/kg group. No adverse effects were detected.
Conclusions and Clinical Relevance—Selamectin was rapidly absorbed transdermally and was rapidly eliminated in rabbits. Results suggested that topical administration at a dosage of 20 mg/kg every 7 days is efficacious for treatment of flea infestation in rabbits. Further studies are needed to assess long-term safety in rabbits following repeated applications.
Abstract
Objective—To determine the pharmacokinetics of marbofloxacin after oral administration every 24 hours to rabbits during a 10-day period.
Animals—8 healthy 9-month-old female New Zealand White rabbits.
Procedures—Marbofloxacin (5 mg/kg) was administered orally every 24 hours to 8 rabbits for 10 days. The first day of administration was designated as day 1. Blood samples were obtained at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 24 hours on days 1 and 10 of marbofloxacin administration. Plasma marbofloxacin concentrations were quantitated by use of a validated liquid chromatography–mass spectrometry assay. Pharmacokinetic analysis of marbofloxacin was analyzed via noncompartmental methods.
Results—After oral administration, mean ± SD area under the curve was 10.50 ± 2.00 μg·h/mL and 10.90 ± 2.45 μg·h/mL, maximum plasma concentration was 1.73 ± 0.35 μg/mL and 2.56 ± 0.71 μg/mL, and harmonic mean terminal half-life was 8.0 hours and 3.9 hours for days 0 and 10, respectively.
Conclusions and Clinical Relevance—Marbofloxacin administered orally every 24 hours for 10 days appeared to be absorbed well and tolerated by rabbits. Administration of marbofloxacin at a dosage of 5 mg/kg, PO, every 24 hours is recommended for rabbits to control infections attributable to susceptible bacteria.
Abstract
Objective—To determine the pharmacokinetics of meloxicam (1 mg/kg) in rabbits after oral administration of single and multiple doses.
Animals—6 healthy rabbits.
Procedures—A single dose of meloxicam (1 mg/kg, PO) was administered to the rabbits. After a 10-day washout period, meloxicam (1 mg/kg, PO) was administered to rabbits every 24 hours for 5 days. Blood samples were obtained from rabbits at predetermined intervals during both treatment periods. Plasma meloxicam concentrations were determined, and noncompartmental pharmacokinetic analysis was performed.
Results—The mean peak plasma concentration and area under the plasma concentration-versus-time curve extrapolated to infinity after administration of a single dose of meloxicam were 0.83 μg/mL and 10.37 h•μg/mL, respectively. After administration of meloxicam for 5 days, the mean peak plasma concentration was 1.33 μg/mL, and the area under the plasma concentration-versus-time curve from the time of administration of the last dose to 24 hours after that time was 18.79 h•μg/mL. For single- and multiple-dose meloxicam experiments, the mean time to maximum plasma concentration was 6.5 and 5.8 hours and the mean terminal half-life was 6.1 and 6.7 hours, respectively.
Conclusions and Clinical Relevance—Plasma concentrations of meloxicam for rabbits in the present study were proportionally higher than those previously reported for rabbits receiving 0.2 mg of meloxicam/kg and were similar to those determined for animals of other species that received clinically effective doses. A dose of 1 mg/kg may be necessary to achieve clinically effective circulating concentrations of meloxicam in rabbits, although further studies are needed.
Abstract
OBJECTIVES
To characterize the pharmacokinetics of a single oral dose (6 mg/kg) of mavacoxib in New Zealand White rabbits (Oryctolagus cuniculus) and to characterize any clinicopathologic effects with this medication and dose.
ANIMALS
Six healthy, 4-month-old New Zealand White rabbits (3 male, 3 female).
PROCEDURES
Before drug administration, clinicopathologic samples were collected for baseline data (CBC, serum biochemical analyses, and urinalysis including urine protein-to-creatinine ratio). All 6 rabbits received a single oral dose (6 mg/kg) of mavacoxib. Clinicopathologic samples were collected at set time intervals to compare with the baseline. Plasma mavacoxib concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using non-compartmental methods.
RESULTS
After a single oral dose, the maximum plasma concentration (Cmax; mean, range) was 854 (713–1040) ng/mL, the time to Cmax (tmax) was 0.36 (0.17–0.50) days, the area under the curve from 0 to the last measured time point (AUC0-last) was 2000 (1765–2307) days*ng/mL, the terminal half-life (t1/2) was 1.63 (1.30–2.26) days, and the terminal rate constant (λz) was 0.42 (0.31–0.53) days. All results for CBCs, serum biochemical analyses, urinalyses, and urine protein-to-creatinine ratios remained within published normal reference intervals.
CLINICAL RELEVANCE
This study determined that plasma concentrations reached target levels of 400 ng/mL for 48 hours in 3/6 rabbits at 6 mg/kg PO. In the remaining 3/6 rabbits, the plasma concentrations were 343–389 ng/mL at 48 hours, which is below the target concentration. Further research is needed to make a dosing recommendation, including a pharmacodynamic study and investigating pharmacokinetics at different doses and multiple doses.
Abstract
Objective—To evaluate the effect of a continuous rate infusion (CRI) of lidocaine on the minimum alveolar concentration (MAC) of isoflurane in rabbits.
Animals—Five 12-month-old female New Zealand White rabbits (Oryctolagus cuniculus).
Procedures—Rabbits were anesthetized with isoflurane. Baseline isoflurane MAC was determined by use of the tail clamp technique. A loading dose of lidocaine (2.0 mg/kg, IV) was administered followed by a CRI of lidocaine at 50 μg/kg/min. After 30 minutes, isoflurane MAC was determined. Another loading dose was administered, and the lidocaine CRI then was increased to 100 μg/kg/min. After 30 minutes, isoflurane MAC was determined again. Plasma samples were obtained for lidocaine analysis after each MAC determination.
Results—Baseline isoflurane MAC was 2.09%, which was similar to previously reported values in this species. Lidocaine CRI at 50 and 100 μg/kg/min induced significant reductions in MAC. The 50 μg/kg/min CRI resulted in a mean plasma lidocaine concentration of 0.654 μg/mL and reduction of MAC by 10.5%. The 100 μg/kg/min CRI of lidocaine resulted in a mean plasma concentration of 1.578 μg/mL and reduction of MAC by 21.7%. Lidocaine also induced significant decreases in arterial blood pressure and heart rate. All cardiopulmonary variables were within reference ranges for rabbits anesthetized with inhalation anesthetics. No adverse effects were detected; all rabbits had an uncomplicated recovery from anesthesia.
Conclusions and Clinical Relevance—Lidocaine administered as a CRI at 50 and 100 μg/kg/min decreased isoflurane MAC in rabbits. The IV administration of lidocaine may be a useful adjunct in anesthesia of rabbits.
Abstract
Objective—To determine the pharmacokinetics and safety of meloxicam in rabbits when administered orally for 29 days.
Animals—6 healthy rabbits.
Procedures—Meloxicam (1.0 mg/kg, PO, q 24 h) was administered to rabbits for 29 days. Blood was collected immediately before (time 0) and 2, 4, 6, 8, and 24 hours after drug administration on days 1, 8, 15, 22, and 29 to evaluate the pharmacokinetics of meloxicam. On day 30, an additional sample was collected 36 hours after treatment. Plasma meloxicam concentrations were quantified with liquid chromatography–mass spectrometry, and noncompartmental pharmacokinetic analysis was performed. Weekly plasma biochemical analyses were performed to evaluate any adverse physiologic effects. Rabbits were euthanatized for necropsy on day 31.
Results—Mean ± SD peak plasma concentrations of meloxicam after administration of doses 1, 8, 15, 22, and 29 were 0.67 ± 0.19 μg/mL, 0.81 ± 0.21 μg/mL, 1.00 ± 0.31 μg/mL, 1.00 ± 0.29 μg/mL, and 1.07 ± 0.19 μg/mL, respectively; these concentrations did not differ significantly among doses 8 through 29. Results of plasma biochemical analyses were within reference ranges at all time points evaluated. Gross necropsy and histologic examination of tissues revealed no clinically relevant findings.
Conclusions and Clinical Relevance—Plasma concentrations of meloxicam for rabbits in the present study were similar to those previously reported in rabbits that received 1. 0 mg of meloxicam/kg, PO every 24 hours, for 5 days. Results suggested that a dosage of 1. 0 mg/kg, PO, every 24 hours for up to 29 days may be safe for use in healthy rabbits.
Abstract
Objective—To determine pharmacokinetics and tissue concentrations of azithromycin in ball pythons ( Python regius ) after IV or oral administration of a single dose.
Animals—2 male and 5 female ball pythons.
Procedures—Using a crossover design, each snake was given a single dose of azithromycin (10 mg/kg) IV. After a 4-week washout period, each snake was given a single dose of azithromycin (10 mg/kg) orally. Blood samples were collected prior to dose administration and 1, 3, 6, 12, 24, 48, 72, and 96 hours after azithromycin administration. Azithromycin was quantitated by use of liquid chromatography-mass spectrometry.
Results—After IV administration, azithromycin had an apparent volume of distribution of 5.69 L/kg and a plasma clearance of 0.19 L/h/kg. Harmonic means for the terminal half-life were 17 hours following IV administration and 51 hours following oral administration. Mean residence times were 37 and 94 hours following IV and oral administration, respectively. Following oral administration, azithromycin had a peak plasma concentration (Cmax) of 1.04 µg/mL, a time to Cmax of 8.4 hours, and a prolonged mean absorption time of 57 hours. Mean oral bioavailability was 77%. Tissue concentrations ranged from 4 to 140 times the corresponding plasma concentration at 24 and 72 hours after azithromycin administration.
Conclusions and Clinical Relevance—Azithromycin is well absorbed and tolerated by ball pythons. On the basis of plasma pharmacokinetics and tissue concentration data, we suggest an azithromycin dosage in ball pythons of 10 mg/kg, orally, every 2 to 7 days, depending upon the site of infection and susceptibil ity of the infective organism. (Am J Vet Res 2003;64:225–228)
