Search Results

You are looking at 31 - 40 of 46 items for

  • Author or Editor: Butch KuKanich x
  • Refine by Access: Content accessible to me x
Clear All Modify Search

Abstract

Objective—To evaluate the antinociceptive effects and duration of action of nalbuphine HCl administered IM on thermal thresholds in Hispaniolan Amazon parrots (Amazona ventralis).

Animals—14 healthy adult Hispaniolan Amazon parrots of unknown sex.

Procedures—3 doses of nalbuphine (12.5, 25, and 50 mg/kg, IM) and saline (0.9% NaCl) solution (control treatment) were evaluated in a blinded complete crossover experimental design by use of foot withdrawal threshold to a noxious thermal stimulus. Baseline data on thermal threshold were generated 1 hour before administration of nalbuphine or saline solution; thermal threshold measurements were obtained 0.5, 1.5, 3, and 6 hours after administration.

Results—Nalbuphine administered IM at 12.5 mg/kg significantly increased the thermal threshold (mean change, 2.4°C), compared with results for the control treatment, and significantly changed thermal threshold for up to 3 hours, compared with baseline results (mean change, 2.6° to 3.8°C). Higher doses of nalbuphine did not significantly change thermal thresholds, compared with results for the control treatment, but had a significant effect, compared with baseline results, for up to 3 and 1.5 hours after administration, respectively.

Conclusions and Clinical Relevance—Nalbuphine administered IM at 12.5 mg/kg significantly increased the foot withdrawal threshold to a thermal noxious stimulus in Hispaniolan Amazon parrots. Higher doses of nalbuphine did not result in significantly increased thermal thresholds or a longer duration of action and would be expected to result in less analgesic effect than lower doses. Further studies are needed to fully evaluate the analgesic effects of nalbuphine in psittacine species.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To describe the pharmacokinetics of N-acetylcysteine (NAC) in healthy cats after oral and IV administration.

Animals—6 healthy cats.

Procedures—In a crossover study, cats received NAC (100 mg/kg) via IV and oral routes of administration; there was a 4-week washout period between treatments. Plasma samples were obtained at 0, 5, 15, 30, and 45 minutes and 1, 2, 4, 8, 12, 24, 36, and 48 hours after administration, and NAC concentrations were quantified by use of a validated high-performance liquid chromatography–mass spectrometry protocol. Data were analyzed via compartmental and noncompartmental pharmacokinetic analysis.

Results—Pharmacokinetics for both routes of administration were best described by a 2-compartment model. Mean ± SD elimination half-life was 0.78 ± 0.16 hours and 1.34 ± 0.24 hours for the IV and oral routes of administration, respectively. Mean bioavailability of NAC after oral administration was 19.3 ± 4.4%.

Conclusions and Clinical Relevance—The pharmacokinetics of NAC for this small population of healthy cats differed from values reported for humans. Assuming there would be similar pharmacokinetics in diseased cats, dose extrapolations from human medicine may result in underdosing of NAC in cats with acute disease. Despite the low bioavailability, plasma concentrations of NAC after oral administration at 100 mg/kg may be effective in the treatment of chronic diseases.

Full access
in American Journal of Veterinary Research

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.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate antinociceptive effects and pharmacokinetics of butorphanol tartrate after IM administration to American kestrels (Falco sparverius).

Animals—Fifteen 2- to 3-year-old American kestrels (6 males and 9 females).

Procedures—Butorphanol (1, 3, and 6 mg/kg) and saline (0.9% NaCl) solution were administered IM to birds in a crossover experimental design. Agitation-sedation scores and foot withdrawal response to a thermal stimulus were determined 30 to 60 minutes before (baseline) and 0.5, 1.5, 3, and 6 hours after treatment. For the pharmacokinetic analysis, butorphanol (6 mg/kg, IM) was administered in the pectoral muscles of each of 12 birds.

Results—In male kestrels, butorphanol did not significantly increase thermal thresholds for foot withdrawal, compared with results for saline solution administration. However, at 1.5 hours after administration of 6 mg of butorphanol/kg, the thermal threshold was significantly decreased, compared with the baseline value. Foot withdrawal threshold for female kestrels after butorphanol administration did not differ significantly from that after saline solution administration. However, compared with the baseline value, withdrawal threshold was significantly increased for 1 mg/kg at 0.5 and 6 hours, 3 mg/kg at 6 hours, and 6 mg/kg at 3 hours. There were no significant differences in mean sedation-agitation scores, except for males at 1.5 hours after administration of 6 mg/kg.

Conclusion and Clinical Relevance—Butorphanol did not cause thermal antinociception suggestive of analgesia in American kestrels. Sex-dependent responses were identified. Further studies are needed to evaluate the analgesic effects of butorphanol in raptors.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetics of hydromorphone hydrochloride after IV and IM administration in American kestrels (Falco sparverius).

Animals—12 healthy adult American kestrels.

Procedures—A single dose of hydromorphone (0.6 mg/kg) was administered IM (pectoral muscles) and IV (right jugular vein); the time between IM and IV administration experiments was 1 month. Blood samples were collected at 5 minutes, 1 hour, and 3 hours (n = 4 birds); 0.25, 1.5, and 9 hours (4); and 0.5, 2, and 6 hours (4) after drug administration. Plasma hydromorphone concentrations were determined by means of liquid chromatography with mass spectrometry, and pharmacokinetic parameters were calculated with a noncompartmental model. Mean plasma hydromorphone concentration for each time was determined with naïve averaged pharmacokinetic analysis.

Results—Plasma hydromorphone concentrations were detectable in 2 and 3 birds at 6 hours after IM and IV administration, respectively, but not at 9 hours after administration. The fraction of the hydromorphone dose absorbed after IM administration was 0.75. The maximum observed plasma concentration was 112.1 ng/mL (5 minutes after administration). The terminal half-life was 1.25 and 1.26 hours after IV and IM administration, respectively.

Conclusion and Clinical Relevance—Results indicated hydromorphone hydrochloride had high bioavailability and rapid elimination after IM administration, with a short terminal half-life, rapid plasma clearance, and large volume of distribution in American kestrels. Further studies regarding the effects of other doses, other administration routes, constantrate infusions, and slow release formulations on the pharmacokinetics of hydromorphone hydrochloride and its metabolites in American kestrels may be indicated.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To quantify plasma concentrations and determine adverse ocular, renal, or hepatic effects associated with repeated topical ophthalmic application of 0.1% diclofenac to healthy cats.

ANIMALS 8 healthy sexually intact male cats.

PROCEDURES A randomized, placebo-controlled crossover study was conducted. A topical formulation of 0.1% diclofenac was administered 4 times/d for 7 days to 4 cats, and artificial tear (control) solution was administered to the other 4 cats. After a 12-day washout period, cats received the other treatment. Ophthalmic examinations were performed daily. Plasma samples were obtained on days 1 and 7 for pharmacokinetic analysis. A CBC, serum biochemical analysis, urinalysis, determination of urine protein-to-creatinine ratio, and determination of glomerular filtration rate were performed before the start of the study and after each 7-day treatment period.

RESULTS Mild conjunctival hyperemia was the only adverse ocular effect detected. Maximal drug concentration and area under the curve were significantly higher on day 7 than on day 1. Diclofenac-treated cats had a significantly lower glomerular filtration rate than did control-treated cats after the second but not after the first treatment period, presumably associated with iatrogenic hypovolemia.

CONCLUSIONS AND CLINICAL RELEVANCE Topical ophthalmic administration of 0.1% diclofenac was well tolerated in healthy cats, with only mild signs of ocular irritation. Detectable systemic concentrations of diclofenac were achieved with accumulation over 7 days. Systemic absorption of diclofenac may be associated with reduced glomerular filtration rate, particularly in volume-contracted animals. Topical ophthalmic 0.1% diclofenac should be used with caution in volume-contracted or systemically ill cats.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine perioperative analgesia associated with oral administration of a novel methadone-fluconazole-naltrexone formulation in dogs undergoing routine ovariohysterectomy.

ANIMALS

43 healthy female dogs.

PROCEDURES

Dogs were randomly assigned to receive the methadone-fluconazole-naltrexone formulation at 1 of 2 dosages (0.5 mg/kg, 2.5 mg/kg, and 0.125 mg/kg, respectively, or 1.0 mg/kg, 5.0 mg/kg, and 0.25 mg/kg, respectively, PO, q 12 h, starting the evening before surgery; n = 15 each) or methadone alone (0.5 mg/kg, SC, q 4 h starting the morning of surgery; 13). Dogs were sedated with acepromazine, and anesthesia was induced with propofol and maintained with isoflurane. A standard ovariohysterectomy was performed by experienced surgeons. Sedation and pain severity (determined with the Glasgow Composite Pain Scale—short form [GCPS-SF]) were scored for 48 hours after surgery. Rescue analgesia was to be provided if the GCPS-SF score was > 6. Dogs also received carprofen starting the day after surgery.

RESULTS

None of the dogs required rescue analgesia. The highest recorded GCPS-SF score was 4. A significant difference in GCPS-SF score among groups was identified at 6:30 am the day after surgery, but not at any other time. The most common adverse effect was perioperative vomiting, which occurred in 11 of the 43 dogs.

CONCLUSIONS AND CLINICAL RELEVANCE

Oral administration of a methadone-fluconazole-naltrexone formulation at either of 2 dosages every 12 hours (3 total doses) was as effective as SC administration of methadone alone every 4 hours (4 total doses) in dogs undergoing routine ovariohysterectomy. Incorporation of naltrexone in the novel formulation may provide a deterrent to human opioid abuse or misuse.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine the effect of age on the pharmacokinetics and pharmacodynamics of flunixin meglumine following IV and transdermal administration to calves.

ANIMALS 8 healthy weaned Holstein bull calves.

PROCEDURES At 2 months of age, all calves received an injectable solution of flunixin (2.2 mg/kg, IV); then, after a 10-day washout period, calves received a topical formulation of flunixin (3.33 mg/kg, transdermally). Blood samples were collected at predetermined times before and for 48 and 72 hours, respectively, after IV and transdermal administration. At 8 months of age, the experimental protocol was repeated except calves received flunixin by the transdermal route first. Plasma flunixin concentrations were determined by liquid chromatography-tandem mass spectroscopy. For each administration route, pharmacokinetic parameters were determined by noncompartmental methods and compared between the 2 ages. Plasma prostaglandin (PG) E2 concentration was determined with an ELISA. The effect of age on the percentage change in PGE2 concentration was assessed with repeated-measures analysis. The half maximal inhibitory concentration of flunixin on PGE2 concentration was determined by nonlinear regression.

RESULTS Following IV administration, the mean half-life, area under the plasma concentration-time curve, and residence time were lower and the mean clearance was higher for calves at 8 months of age than at 2 months of age. Following transdermal administration, the mean maximum plasma drug concentration was lower and the mean absorption time and residence time were higher for calves at 8 months of age than at 2 months of age. The half maximal inhibitory concentration of flunixin on PGE2 concentration at 8 months of age was significantly higher than at 2 months of age. Age was not associated with the percentage change in PGE2 concentration following IV or transdermal flunixin administration.

CONCLUSIONS AND CLINICAL RELEVANCE In calves, the clearance of flunixin at 2 months of age was slower than that at 8 months of age following IV administration. Flunixin administration to calves may require age-related adjustments to the dose and dosing interval and an extended withdrawal interval.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine pharmacokinetic and pharmacodynamic properties of the injectable formulation of dexmedetomidine administered via the oral transmucosal (OTM) route to healthy dogs.

ANIMALS

6 healthy dogs.

PROCEDURES

Injectable dexmedetomidine was administered IV (5 μg/kg) or via the OTM route (20 μg/kg) in a blinded, single-observer, randomized crossover study. Dogs received dexmedetomidine and a sham treatment at each administration. Serial blood samples were collected from a catheter in a saphenous vein. Heart rate, respiratory rate, and subjective sedation score were assessed for 24 hours after administration. Plasma samples were analyzed for dexmedetomidine concentrations by use of ultraperformance liquid chromatography–tandem mass spectrometry.

RESULTS

For the OTM route, the mean ± SD maximum plasma concentration was 3.8 ± 1.3 ng/mL, which was detected 73 ± 33 minutes after administration. The mean maximum concentration for the IV dose, when extrapolated to the time of administration, was 18.6 ± 3.3 ng/mL. The mean terminal-phase half-life was 152 ± 146 minutes and 36 ± 6 minutes for OTM and IV administration, respectively. After IV administration, total clearance was 8.0 ± 1.6 mL/min/kg and volume of distribution at steady state was 371 ± 72 mL/kg. Bioavailability for OTM administration of dexmedetomidine was 11.2 ± 4.5%. Peak sedation scores did not differ significantly between routes of administration. Decreases in heart rate, respiratory rate, and peak sedation score were evident sooner after IV administration.

CONCLUSIONS AND CLINICAL RELEVANCE

OTM administration of the injectable formulation of dexmedetomidine resulted in a similar degree of sedation and prolonged duration of action, compared with results for IV administration, despite relatively low bioavailability.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine effects of fentanyl, lidocaine, and a fentanyl-lidocaine combination on the minimum alveolar concentration of sevoflurane preventing motor movement (MACNM) in dogs.

ANIMALS 6 adult Beagles.

PROCEDURES Dogs were anesthetized with sevoflurane in oxygen 3 times (1-week intervals). Baseline MACNM (MACNM-B) was determined starting 45 minutes after induction of anesthesia. Dogs then received 1 of 3 treatments IV: fentanyl (loading dose, 15 μg/kg; constant rate infusion [CRI], 6 μg/kg/h), lidocaine (loading dose, 2 mg/kg; CRI, 6 mg/kg/h), and the fentanyl-lidocaine combination at the same doses. Determination of treatment MACNM (MACNM-T) was initiated 90 minutes after start of the CRI. Venous blood samples were collected at the time of each treatment MACNM measurement for determination of plasma concentrations of fentanyl and lidocaine.

RESULTS Mean ± SEM overall MACNM-B for the 3 treatments was 2.70 ± 0.27 vol%. The MACNM decreased from MACNM-B to MACNM-T by 39%, 21%, and 55% for fentanyl, lidocaine, and the fentanyl-lidocaine combination, respectively. This decrease differed significantly among treatments. Plasma fentanyl concentration was 3.25 and 2.94 ng/mL for fentanyl and the fentanyl-lidocaine combination, respectively. Plasma lidocaine concentration was 2,570 and 2,417 ng/mL for lidocaine and the fentanyl-lidocaine combination, respectively. Plasma fentanyl and lidocaine concentrations did not differ significantly between fentanyl and the fentanyl-lidocaine combination or between lidocaine and the fentanyl-lidocaine combination.

CONCLUSIONS AND CLINICAL RELEVANCE CRIs of fentanyl, lidocaine, and the fentanyl-lidocaine combination at the doses used were associated with clinically important and significant decreases in the MACNM of sevoflurane in dogs.

Full access
in American Journal of Veterinary Research