Objective—To determine the pharmacokinetics of tramadol and its metabolites O-desmethyltramadol (ODT) and N-desmethyltramadol (NDT) in adult horses.
Animals—12 mixed-breed horses.
Procedures—Horses received tramadol IV (5 mg/kg, over 3 minutes) and orally (10 mg/kg) with a 6-day washout period in a randomized crossover design. Serum samples were collected over 48 hours. Serum tramadol, ODT, and NDT concentrations were measured via high-performance liquid chromatography and analyzed via noncompartmental analysis.
Results—Maximum mean ± SEM serum concentrations after IV administration for tramadol, ODT, and NDT were 5,027 ± 638 ng/mL, 0 ng/mL, and 73.7 ± 12.9 ng/mL, respectively. For tramadol, half-life, volume of distribution, area under the curve, and total body clearance after IV administration were 2.55 ± 0.88 hours, 4.02 ± 1.35 L/kg, 2,701 ± 275 h•ng/mL, and 30.1 ± 2.56 mL/min/kg, respectively. Maximal serum concentrations after oral administration for tramadol, ODT, and NDT were 238 ± 41.3 ng/mL, 86.8 ± 17.8 ng/mL, and 159 ± 20.4 ng/mL, respectively. After oral administration, half-life for tramadol, ODT, and NDT was 2.14 ± 0.50 hours, 1.01 ± 0.15 hours, and 2.62 ± 0.49 hours, respectively. Bioavailability of tramadol was 9.50 ± 1.28%. After oral administration, concentrations achieved minimum therapeutic ranges for humans for tramadol (> 100 ng/mL) and ODT (> 10 ng/mL) for 2.2 ± 0.46 hours and 2.04 ± 0.30 hours, respectively.
Conclusions and Clinical Relevance—Duration of analgesia after oral administration of tramadol might be < 3 hours in horses, with ODT and the parent compound contributing equally.
To characterize the pharmacokinetics of a clinically relevant dose of misoprostol administered PO or per rectum (PR) to horses.
8 healthy adult horses.
In a randomized 3-way crossover design, horses received a single dose of misoprostol (5 μg/kg) administered PO (with horses fed and unfed) and PR, with a minimum 3-week washout period separating the experimental conditions. Blood samples were obtained before and at various points after drug administration (total, 24 hours), and plasma concentrations of misoprostol free acid were measured.
Mean maximum plasma concentration of misoprostol was significantly higher in the PR condition (mean ± SD, 967 ± 492 pg/mL) and unfed PO condition (655 ± 259 pg/mL) than in the fed PO condition (352 ± 109 pg/mL). Mean area under the concentration-versus-time curve was significantly lower in the PR condition (219 ± 131 pg•h/mL) than in the unfed (1,072 ± 360 pg•h/mL) and fed (518 ± 301 pg•h/mL) PO conditions. Mean time to maximum concentration was ≤ 30 minutes for all conditions. Mean disappearance half-life was shortest in the PR condition (21 ± 29 minutes), compared with values for the unfed (170 ± 129 minutes) and fed (119 ± 51 minutes) PO conditions. No adverse effects were noted.
CONCLUSIONS AND CLINICAL RELEVANCE
Misoprostol was rapidly absorbed and eliminated regardless of whether administered PO or PR to horses. Rectal administration may be a viable alternative for horses that cannot receive misoprostol PO, but this route may require more frequent administration to maintain therapeutic drug concentrations.
OBJECTIVE To determine pharmacokinetics after oral administration of single and multiple doses and to assess the safety of zonisamide in Hispaniolan Amazon parrots (Amazona ventralis).
ANIMALS 12 adult Hispaniolan Amazon parrots.
PROCEDURES Zonisamide (30 mg/kg, PO) was administered once to 6 parrots in a single-dose trial. Six months later, a multiple-dose trial was performed in which 8 parrots received zonisamide (20 mg/kg, PO, q 12 h for 10 days) and 4 parrots served as control birds. Safety was assessed through monitoring of body weight, attitude, and urofeces and comparison of those variables and results of CBC and biochemical analyses between control and treatment groups.
RESULTS Mean ± SD maximum plasma concentration of zonisamide for the single- and multiple-dose trials was 21.19 ± 3.42 μg/mL at 4.75 hours and 25.11 ± 1.81 μg/mL at 2.25 hours after administration, respectively. Mean plasma elimination half-life for the single- and multiple-dose trials was 13.34 ± 2.10 hours and 9.76 ± 0.93 hours, respectively. Pharmacokinetic values supported accumulation in the multiple-dose trial. There were no significant differences in body weight, appearance of urofeces, or appetite between treated and control birds. Although treated birds had several significant differences in hematologic and biochemical variables, all variables remained within reference values for this species.
CONCLUSIONS AND CLINICAL RELEVANCE Twice-daily oral administration of zonisamide to Hispaniolan Amazon parrots resulted in plasma concentrations known to be therapeutic in dogs without evidence of adverse effects on body weight, attitude, and urofeces or clinically relevant changes to hematologic and biochemical variables.