To determine an optimal ceftazidime dosing strategy in Northern leopard frogs (Lithobates pipiens) by evaluation of 2 different doses administered SC and 1 dose administered transcutaneously.
44 Northern leopard frogs (including 10 that were replaced).
Ceftazidime was administered to frogs SC in a forelimb at 20 mg/kg (n = 10; SC20 group) and 40 mg/kg (10; SC40 group) or transcutaneously on the cranial dorsum at 20 mg/kg (10; TC20 group). Two frogs in each ceftazidime group were euthanized 12, 24, 48, 72, and 96 hours after drug administration. Plasma, renal, and skin concentrations of ceftazidime were measured by means of reversed-phase high-performance liquid chromatography. Four control frogs were used for assay validation.
Mean plasma half-life of ceftazidime in the SC20, SC40, and TC20 groups was 9.01 hours, 14.49 hours, and too low to determine, respectively. Mean maximum plasma ceftazidime concentration was 92.9, 96.0, and 1.3 μg/mL, respectively. For 24 hours after drug administration in the SC20 and SC40 groups, plasma ceftazidime concentration exceeded 8 μg/mL. Renal and skin concentrations were detectable at both doses and routes of administration; however, skin concentrations were significantly lower than renal and plasma concentrations.
CONCLUSIONS AND CLINICAL RELEVANCE
Findings indicated that ceftazidime administration to Northern leopard frogs at 20 mg/kg, SC, every 24 hours would achieve a plasma concentration exceeding the value considered effective against common amphibian pathogens. Transcutaneous administration of the injectable ceftazidime formulation at 20 mg/kg warrants further investigation but is not currently recommended because of a potential lack of efficacy.
OBJECTIVE To determine pharmacokinetics after IM and oral administration of a single dose of meloxicam to American flamingos (Phoenicopertus ruber).
ANIMALS 14 adult flamingos.
PROCEDURES Flamingos were allocated to 2 groups. Each group received a dose of meloxicam (1 mg/kg) by the IM or oral route. After a 4-week washout period, groups received meloxicam via the other route of administration. Plasma meloxicam concentrations were measured with high-performance liquid chromatography. Data for each bird were analyzed. Estimated values of selected pharmacokinetic parameters were compared by use of a linear mixed-effects ANOVA. Pooled concentration-time profiles for each route of administration were analyzed to examine the influence of body weight on pharmacokinetics.
RESULTS Mean ± SD maximum plasma concentration was 1.00 ± 0.88 μg/mL after oral administration. This was approximately 15% of the mean maximum plasma concentration of 5.50 ± 2.86 μg/mL after IM administration. Mean time to maximum plasma concentration was 1.33 ± 1.32 hours after oral administration and 0.28 ± 0.17 hours after IM administration. Mean half-life of the terminal phase after oral administration (3.83 ± 2.64 hours) was approximately twice that after IM administration (1.83 ± 1.22 hours).
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the extent and rate of meloxicam absorption were less after oral administration than after IM administration. Intramuscular administration resulted in a short period during which mean plasma concentrations met or exceeded reported efficacious analgesic concentrations in other species, whereas oral administration did not. These results suggested that higher doses may be required for oral administration.
Objective—To determine the pharmacokinetics of an orally administered dose of tramadol in domestic rabbits (Oryctolagus cuniculus).
Animals—6 healthy adult sexually intact female New Zealand White rabbits.
Procedures—Physical examinations and plasma biochemical analyses were performed to ensure rabbits were healthy prior to the experiment. Rabbits were anesthetized with isoflurane, and IV catheters were placed in a medial saphenous or jugular vein for collection of blood samples. One blood sample was collected before treatment with tramadol. Rabbits were allowed to recover from anesthesia a minimum of 1 hour before treatment. Then, tramadol (11 mg/kg, PO) was administered once, and blood samples were collected at various time points up to 360 minutes after administration. Blood samples were analyzed with high-performance liquid chromatography to determine plasma concentrations of tramadol and its major metabolite (O-desmethyltramadol).
Results—No adverse effects were detected after oral administration of tramadol to rabbits. Mean ± SD half-life of tramadol after administration was 145.4 ± 81.0 minutes; mean ± SD maximum plasma concentration was 135.3 ± 89.1 ng/mL.
Conclusions and Clinical Relevance—Although the dose of tramadol required to provide analgesia in rabbits is unknown, the dose administered in the study reported here did not reach a plasma concentration of tramadol or O-desmethyltramadol that would provide sufficient analgesia in humans for clinically acceptable periods. Many factors may influence absorption of orally administered tramadol in rabbits.
OBJECTIVE To determine the pharmacokinetics of chloramphenicol base after PO administration at a dose of SO mg/kg (22.7 mg/lb) in adult horses from which food was not withheld.
DESIGN Prospective crossover study.
ANIMALS 5 adult mares.
PROCEDURES Chloramphenicol base (SO mg/kg) was administered PO to each horse, and blood samples were collected prior to administration (0 minutes) and at 5, 10, 15, and 30 minutes and 1, 2, 4, 8, and 12 hours thereafter. Following a washout period, chloramphenicol sodium succinate (25 mg/kg [11.4 mg/lb]) was administered IV to each horse, and blood samples were collected prior to administration (0 minutes) and at 3, 5, 10, 15, 30, and 45 minutes and 1, 2, 4, and 8 hours thereafter.
RESULTS In horses, plasma half-life, volume of distribution at steady state, clearance, and area under the plasma concentration-time curve for chloramphenicol after IV administration ranged from 0.65 to 1.20 hours, 0.51 to 0.78 L/kg, 0.78 to 1.22 L/h/kg, and 20.5 to 32.1 h·μg/mL, respectively. The elimination half-life, time to maximum plasma concentration, maximum plasma concentration, and area under the plasma concentration-time curve after PO administration ranged from 1.7 to 7.4 hours, 0.25 to 2.00 hours, 1.52 to 5.45 μg/mL, and 10.3 to 21.6 h·μg/mL, respectively. Mean ± SD chloramphenicol bioavailability was 28 ± 10% and terminal half-life was 2.85 ± 1.32 hours following PO administration.
CONCLUSIONS AND CLINICAL RELEVANCE Given that the maximum plasma chloramphenicol concentration in this study was lower than previously reported values, it is recommended to determine the drug's MIC for target bacteria before administration of chloramphenicol in adult horses.
Objective—To compare pharmacokinetics after a single IM or SC injection of ceftiofur crystalline-free acid (CCFA) to bearded dragons (Pogona vitticeps).
Animals—8 adult male bearded dragons.
Procedures—In a preliminary experiment, doses of 15 and 30 mg/kg, SC, were compared in 2 animals, and 30 mg/kg resulted in a more desirable pharmacokinetic profile. Then, in a randomized, complete crossover experimental design, each bearded dragon (n = 6) received a single dose of 30 mg of CCFA/kg IM or SC; the experiment was repeated after a 28-day washout period with the other route of administration. Blood samples were collected at 10 time points for 288 hours after injection. Plasma concentrations of ceftiofur and desfuroylceftiofur metabolites were measured via reverse-phase high-performance liquid chromatography. Data were analyzed with a noncompartmental model.
Results—No adverse effects were observed. Plasma concentrations greater than a target minimum inhibitory concentration of 1 μg/mL were achieved by 4 hours after administration by both routes. Mean plasma concentrations remained > 1 μg/mL for > 288 hours for both routes of administration.
Conclusions and Clinical Relevance—A single dose of CCFA (30 mg/kg) administered IM or SC to bearded dragons yielded plasma concentrations of ceftiofur and its metabolites > 1 μg/mL for > 288 hours. The SC route would be preferred because of less variability in plasma concentrations and greater ease of administration than the IM route. Future studies should include efficacy data as well as evaluation of the administration of multiple doses.
Objective—To determine ocular tissue drug concentrations after topical ocular administration of 0.3% ciprofloxacin and 0.5% moxifloxacin in ophthalmologically normal horses.
Animals—24 ophthalmologically normal adult horses.
Procedures—0.3% ciprofloxacin and 0.5% moxifloxacin solutions (0.1 mL) were applied to the ventral conjunctival fornix of 1 eye in each horse as follows: group 1 (n = 8) at 0, 2, 4, and 6 hours; group 2 (8) at 0, 2, 4, 6, and 10 hours; and group 3 (8) at 0, 2, 4, 6, 10, and 14 hours. Tears, cornea, and aqueous humor (AH) were collected at 8, 14, and 18 hours for groups 1, 2, and 3, respectively. Drug concentrations were determined via high-performance liquid chromatography.
Results—Median (25th to 75th percentile) concentrations of ciprofloxacin for groups 1, 2, and 3 in tears (μg/mL) were 53.7 (25.5 to 88.8), 48.5 (19.7 to 74.7), and 24.4 (15.4 to 67.1), respectively; in corneal tissue (μg/g) were 0.95 (0.60 to 1.02), 0.37 (0.32 to 0.47), and 0.48 (0.34 to 0.95), respectively; and in AH were lower than the limit of quantification in all groups. Concentrations of moxifloxacin for groups 1, 2, and 3 in tears (μg/mL) were 188.7 (44.5 to 669.2), 107.4 (41.7 to 296.5), and 178.1 (70.1 to 400.6), respectively; in corneal tissue (μg/g) were 1.84 (1.44 to 2.11), 0.78 (0.55 to 0.98), and 0.77 (0.65 to 0.97), respectively; and in AH (μg/mL) were 0.06 (0.04 to 0.08), 0.03 (0.02 to 0.05), and 0.02 (0.01 to 0.04), respectively. Corneal moxifloxacin concentrations were significantly higher in group 1 than groups 2 and 3.
Conclusions and Clinical Relevance—After topical ocular administration, fluoroquinolones can reach therapeutic concentrations in tears and corneal tissue of horses, even when there is an intact epithelium.
Objective—To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).
Animals—9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex).
Procedures—Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from −5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from −5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography.
Results—Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were < 40 ng/mL for the entire time period, but oral administration at a dose of 30 mg/kg resulted in mean plasma concentrations > 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration.
Conclusions and Clinical Relevance—Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.
Objective—To evaluate the influence of acidifying or alkalinizing diets on bone mineral density and urine relative supersaturation (URSS) with calcium oxalate and struvite in healthy cats.
Animals—6 castrated male and 6 spayed female cats.
Procedures—3 groups of 4 cats each were fed diets for 12 months that differed only in acidifying or alkalinizing properties (alkalinizing, neutral, and acidifying). Body composition was estimated by use of dual energy x-ray absorptiometry, and 48-hour urine samples were collected for URSS determination.
Results—Urine pH differed significantly among diet groups, with the lowest urine pH values in the acidifying diet group and the highest values in the alkalinizing diet group. Differences were not observed in other variables except urinary ammonia excretion, which was significantly higher in the neutral diet group. Calcium oxalate URSS was highest in the acidifying diet group and lowest in the alkalinizing diet group; struvite URSS was not different among groups. Diet was not significantly associated with bone mineral content or density.
Conclusions and Clinical Relevance—Urinary undersaturation with calcium oxalate was achieved by inducing alkaluria. Feeding an alkalinizing diet was not associated with URSS with struvite. Bone mineral density and calcium content were not adversely affected by diet; therefore, release of calcium from bone caused by feeding an acidifying diet may not occur in healthy cats.
Procedures—A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography.
Results—Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed.
Conclusions and Clinical Relevance—Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.
Objective—To evaluate the effect of IV administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane (ISOMAC) that prevented purposeful movement of rabbits in response to a noxious stimulus.
Animals—Six 6- to 12-month-old female New Zealand White rabbits.
Procedures—Anesthesia was induced and maintained with isoflurane in oxygen. A baseline ISOMAC was determined by clamping a pedal digit with sponge forceps until gross purposeful movement was detected or a period of 60 seconds elapsed. Subsequently, tramadol (4.4 mg/kg) was administered IV and the posttreatment ISOMAC (ISOMACT) was measured.
Results—Mean ± SD ISOMAC and ISOMACT values were 2.33 ± 0.13% and 2.12 ± 0.17%, respectively. The ISOMAC value decreased by 9 ± 4% after tramadol was administered. Plasma tramadol and its major metabolite (M1) concentrations at the time of ISOMACT determination varied widely (ranges, 181 to 636 ng/mL and 32 to 61 ng/mL, respectively). Intervals to determination of ISOMACT and plasma tramadol and M1 concentrations were not correlated with percentage change in the ISOMAC. Heart rate decreased significantly immediately after tramadol administration but by 10 minutes afterward was not different from the pretreatment value. Systolic arterial blood pressure decreased to approximately 60 mm Hg for approximately 5 minutes in 3 rabbits after tramadol administration. No adverse effects were detected.
Conclusions and Clinical Relevance—As administered, tramadol had a significant but clinically unimportant effect on the ISOMAC in rabbits. Higher doses of tramadol may provide clinically important reductions but may result in a greater degree of cardiovascular depression.