Refine search
Results 1-4 of 4
Pharmacokinetic evaluation of novel midazolam gel formulations following buccal administration to healthy dogs
2018
Aldawsari, Mohammed F. | Lau, Vivian W. | Babu, Ramapuram J. | Arnold, Robert D. | Platt, Simon R.
OBJECTIVE To determine the physiochemical properties and pharmacokinetics of 3 midazolam gel formulations following buccal administration to dogs. ANIMALS 5 healthy adult hounds. PROCEDURES In phase 1 of a 2-phase study, 2 gel formulations were developed that contained 1% midazolam in a poloxamer 407 (P1) or hydroxypropyl methylcellulose (H1) base and underwent rheological and in vitro release analyses. Each formulation was buccally administered to 5 dogs such that 0.3 mg of midazolam/kg was delivered. Each dog also received midazolam hydrochloride (0.3 mg/kg, IV). There was a 3-day interval between treatments. Blood samples were collected immediately before and at predetermined times for 8 hours after drug administration for determination of plasma midazolam concentration and pharmacokinetic analysis. During phase 2, a gel containing 2% midazolam in a hydroxypropyl methylcellulose base (H2) was developed on the basis of phase 1 results. That gel was buccally administered such that midazolam doses of 0.3 and 0.6 mg/kg were delivered. Each dog also received midazolam (0.3 mg/kg, IV). All posttreatment procedures were the same as those for phase 1. RESULTS The H1 and H2 formulations had lower viscosity, greater bioavailability, and peak plasma midazolam concentrations that were approximately 2-fold as high, compared with those for the P1 formulation. The mean peak plasma midazolam concentration for the H2 formulation was 187.0 and 106.3 ng/mL when the midazolam dose administered was 0.6 and 0.3 mg/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that buccal administration of gel formulations might be a viable alternative for midazolam administration to dogs.
Show more [+] Less [-]Pharmacokinetics and pharmacodynamics of oral pradofloxacin administration in dogs
2018
Boothe, Dawn M. | Bush, Kaleigh M. | Boothe, Harry W. | Davis, Heather A.
OBJECTIVE To determine whether target values for pharmacokinetic-pharmacodynamic (PK-PD) indices against selected canine pathogens were achievable for pradofloxacin in various canine fluids and leukocytes. ANIMALS 8 healthy adult hounds (experiments 1 and 2) and 6 healthy adult dogs (experiment 3). PROCEDURES In 3 experiments, pradofloxacin (3, 6, or 12 mg/kg) and enrofloxacin (5 or 10 mg/kg) were orally administered once a day for 5 days, and blood, interstitial fluid (ISF), and other fluid samples were collected at various points. Sample drug concentrations were measured, and noncompartmental pharmacokinetic analysis was performed; then, PK-PD indices (ratios between maximum observed concentration [Cmax] and minimum inhibitory or mutant prevention concentrations) were determined for 7 bacterial species. RESULTS PK-PD values for pradofloxacin at 3 mg/kg were approximately 5 times as high in leukocyte versus plasma and were lowest in CSF, synovial fluid, and aqueous humor. No significant differences were noted between serum and ISF. Value ratios for serum versus other body fluids were numerically higher for pradofloxacin (vs enrofloxacin) for all fluid types except CSF and aqueous humor. Target PK-PD values were exceeded for pradofloxacin against all 7 bacterial species in leukocytes and against all species except Bacteroides spp in serum and ISF. Enrofloxacin achieved the target Cmax-to-minimum inhibitory concentration ratio against Pasteurella multocida in serum, ISF, and leukocytes and for Staphylococcus pseudintermedius in serum and leukocytes. A Cmax-to-mutant prevention concentration ratio ≥ 1 against Eschericha coli was achieved for pradofloxacin at 6 mg/kg. CONCLUSIONS AND CLINICAL RELEVANCE These findings supported once-daily oral administration of pradofloxacin to dogs at the currently recommended dose (7.5 mg/kg).
Show more [+] Less [-]Comparison of ultrasound-guided and landmark-based techniques for central venous catheterization via the external jugular vein in healthy anesthetized dogs
2018
OBJECTIVE To compare time to achieve vascular access (TTVA) between an ultrasound-guided technique (UST) and landmark-based technique (LMT) for central venous catheter (CVC) placement in healthy anesthetized dogs. ANIMALS 39 purpose-bred hounds. PROCEDURES Anesthetized dogs that were hemodynamically stable following completion of a terminal surgical exercise were enrolled in the study during 2 phases, with a 45-day intermission between phases. For each dog, a UST and LMT were used for CVC placement via each external jugular vein by 2 operators (criticalist and resident). The TTVA and number of venipuncture attempts and catheter redirections were recorded for each catheterization. Placement of the CVC was confirmed by contrast fluoroscopy. After euthanasia, a gross dissection was performed during which a hematoma score was assigned to the catheter insertion site. For each phase, nonlinear least squares estimation was used for learning curve analysis of the UST. RESULTS Median TTVA, number of venipuncture attempts and catheter redirections, and hematoma score did not differ significantly between the 2 operators for either technique. Median TTVA for the UST (45 seconds) was significantly longer than that for the LMT (7 seconds). Learning curve analysis indicated that 8 and 7 UST catheterizations were required to achieve performance stability in phases 1 and 2, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the UST was comparable to the LMT for CVC placement in healthy dogs. The extra time required to perform the UST was not clinically relevant. Additional studies evaluating the UST for CVC placement in clinically ill dogs are warranted.
Show more [+] Less [-]Feasibility of near-infrared fluorescence imaging for sentinel lymph node evaluation of the oral cavity in healthy dogs
2018
Townsend, Katy L. | Milovancev, Milan | Brach, Shay
OBJECTIVE To evaluate the usefulness of injection of indocyanine green (ICG) solution with near-infrared (NIR) fluorescence imaging for transcutaneous detection of sentinel lymph nodes (SLNs) and their associated lymphatic vessels in the oral mucosa of healthy dogs. ANIMALS 6 adult purpose-bred research hounds. PROCEDURES Each dog was sedated, and 1 mL of ICG solution was injected into the gingival mucosa dorsal to the right maxillary canine tooth. Subsequently, NIR fluorescence imaging was used to transcutaneously detect the lymphatic vessels and SLNs. The distance between the injection site and each SLN was measured. Time to first evidence of node fluorescence was recorded, and velocity of ICG movement was calculated. A slide preparation of a fine-needle aspiration sample of the fluorescing structure underwent cytologic examination (to confirm presence of lymphatic tissue) and NIR fluorescence imaging (to confirm presence of ICG). RESULTS The ipsilateral mandibular lymphocentrum was the SLN in all dogs. The time to visually detectable fluorescence ranged from 4 to 15 minutes (mean ± SD, 8.8 ± 3.76 minutes). The mean velocity was 1.94 ± 0.93 cm/min. Fluorescence was not observed in the contralateral lymph nodes. Each fluorescing structure was confirmed to be lymphatic tissue, and NIR fluorescence imaging revealed that ICG was present in the sampled SLN. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that injection of ICG solution with NIR fluorescence imaging can be used to transcutaneously identify SLNs along with associated lymphatic vessels in the oral mucosa of healthy dogs. Time from injection to identification of fluorescence was rapid with prolonged retention of material within the SLN, indicating that this procedure could be performed during surgery.
Show more [+] Less [-]