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Pharmacokinetics of a single dose of voriconazole administered orally with and without food to red-tailed hawks (Buteo jamaicensus)
2017
Parlsey, Ruth A. | Tell, Lisa A. | Gehring, Ronette
OBJECTIVE To determine the pharmacokinetics of voriconazole administered PO with or without food to red-tailed hawks (Buteo jamaicensus) and whether any observed variability could be explained by measured covariates to inform dose adjustments. ANIMALS 7 adult red-tailed hawks. PROCEDURES In a crossover study design, hawks were randomly assigned to first receive voriconazole (15 mg/kg, PO) injected into a dead mouse (n = 3; fed birds) or without food (4; unfed birds). Sixteen days later, treatments were reversed. Blood samples were collected at various points to measure plasma voriconazole concentrations by ultraperformance liquid chromatography. Pharmacokinetic data were analyzed by noncompartmental methods and fit to a compartmental model through nonlinear mixed-effects regression, with feeding status and body weight investigated as covariates. RESULTS Voriconazole was well absorbed, with quantifiable plasma concentrations up to 24 hours after administration. Mean plasma half-life was approximately 2 hours in fed and unfed birds. Administration of the voriconazole in food delayed absorption, resulting in a significant delay in time to maximum plasma concentration. The final compartmental model included a categorical covariate to account for this lag in absorption as well as body weight as a covariate of total body clearance (relative to unknown bioavailability). CONCLUSIONS AND CLINICAL RELEVANCE A single dose of voriconazole (15 mg/kg) administered PO to red-tailed hawks resulted in mean plasma voriconazole concentrations greater than the targeted value (1 μg/mL). Additional studies with larger sample sizes and multidose regimens are required before the model developed here can be applied in clinical settings.
Show more [+] Less [-]Biomechanical evaluation of two plating configurations for fixation of a simple transverse caudal mandibular fracture model in cats
2017
Greiner, Christopher L. | Verstraete, Frank J. M. | Stover, Susan M. | Garcia, Tanya C. | Leale, Dustin | Arzi, Boaz
OBJECTIVE To evaluate biomechanical properties of intact feline mandibles, compared with those for mandibles with an experimentally created osteotomy that was stabilized with 1 of 2 internal fixation configurations. SAMPLE 20 mandibles from 10 adult feline cadavers. PROCEDURES An incomplete block study design was used to assign the mandibles of each cadaver to 2 of 3 groups (locking plate with locking screws [locking construct], locking plate with nonlocking screws [nonlocking construct], or intact). Within each cadaver, mandibles were randomly assigned to the assigned treatments. For mandibles assigned to the locking and nonlocking constructs, a simple transverse osteotomy was created caudal to the mandibular first molar tooth after plate application. All mandibles were loaded in cantilever bending in a single-load-to-failure test while simultaneously recording load and actuator displacement. Mode of failure (bone or plate failure) was recorded, and radiographic evidence of tooth root and mandibular canal damage was evaluated. Mechanical properties were compared among the 3 groups. RESULTS Stiffness, bending moments, and most post-yield energies for mandibles with the locking and nonlocking constructs were significantly lower than those for intact mandibles. Peak bending moment and stiffness for mandibles with the locking construct were significantly greater than those for mandibles with the nonlocking construct. Mode of failure and frequency of screw damage to tooth roots and the mandibular canal did not differ between the locking and nonlocking constructs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that both fixation constructs were mechanically inferior to intact mandibles. The locking construct was mechanically stronger than the nonlocking construct.
Show more [+] Less [-]Antinociceptive efficacy of intramuscular administration of morphine sulfate and butorphanol tartrate in tegus (Salvator merianae)
2017
Leal, William P. | Carregaro, Adriano B. | Bressan, Thais F. | Bisetto, Shayne P. | Melo, Cristiano F. | Sladky, Kurt K.
OBJECTIVE To evaluate the antinociceptive efficacy of IM morphine sulfate or butorphanol tartrate administration in tegus (Salvator merianae). ANIMALS 6 healthy juvenile (12- to 24-month-old) tegus (mean ± SD body weight, 1,484 ± 473 g). PROCEDURES In a crossover study design, tegus were randomly assigned to treatment order, with a minimum washout period of 15 days between treatments. Each of 5 treatments was administered IM in a forelimb: saline (0.9% NaCl) solution (0.5 mL), morphine sulfate (5 or 10 mg/kg), or butorphanol tartrate (5 or 10 mg/kg). A withdrawal latency test was used to evaluate antinociception, with a noxious thermal stimulus applied to the plantar surface of the hind limb before (0 hours; baseline) and 0.5, 1, 2, 3, 4, 6, 12, and 24 hours after each treatment. Observers were unaware of treatment received. RESULTS With saline solution, mean hind limb withdrawal latencies (interval to limb withdrawal from the thermal stimulus) remained constant, except at 12 hours. Tegus had higher than baseline mean withdrawal latencies between 0.5 and 1 hour and at 12 hours with morphine at 5 mg/kg and between 1 and 12 hours with morphine at 10 mg/kg. With butorphanol at 5 and 10 mg/kg, tegus maintained withdrawal responses similar to baseline at all assessment points. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that morphine, but not butorphanol, provided antinociception at 5 and 10 mg/kg in tegus as measured by thermal noxious stimulus testing. These data supported the hypothesis that μ-opioid (but not κ-opioid) receptor agonists provide antinociception in reptiles.
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