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Abstract

Objective—To determine the pharmacokinetics of marbofloxacin after oral administration in juvenile harbor seals (Phoca vitulina) at a dose of 5 mg/kg (2.3 mg/lb) and to compare pharmacokinetic variables after pharmacokinetic analysis by naïve averaged, naïve pooled, and nonlinear mixed-effects modeling.

Design—Original study.

Animals—33 male and 22 female juvenile seals being treated for various conditions.

Procedures—Blood collection was limited to ≤ 3 samples/seal. Plasma marbofloxacin concentrations were measured via high-pressure liquid chromatography with UV detection.

Results—Mean ± SE dose of marbofloxacin administered was 5.3 ± 0.1 mg/kg (2.4 ± 0.05 mg/lb). The terminal half-life, volume of distribution (per bioavailability), and clearance (per bioavailability) were approximately 5 hours, approximately 1.4 L/kg, and approximately 3 mL/min/kg, respectively (values varied slightly with the method of calculation). Maximum plasma concentration and area under the plasma-time concentration curve were approximately 3 μg/mL and 30 h·μg/mL, respectively. Naïve averaged and naïve pooled analysis appeared to yield a better fit to the population, but nonlinear mixed-effects modeling yielded a better fit for individual seals.

Conclusions and Clinical Relevance—Values of pharmacokinetic variables were similar regardless of the analytic method used. Pharmacokinetic variability can be assessed with nonlinear mixed-effects modeling, but not with naïve averaged or naïve pooled analysis. Visual observation by experienced trainers revealed no adverse effects in treated seals. Plasma concentrations attained with a dosage of 5 mg/kg every 24 hours would be expected to be efficacious for treatment of infections caused by susceptible bacteria (excluding Pseudomonas aeruginosa).

Full access
in Journal of the American Veterinary Medical Association

Abstract

Objective—To determine the pharmacokinetics of morphine after IM administration in a clinical population of horses.

Design—Prospective clinical study.

Animals—77 horses.

Procedures—Morphine sulfate (0.1 mg/kg [0.045 mg/lb], IM) was administered to horses, and blood samples were obtained at predetermined time points. Plasma morphine concentrations were measured via liquid chromatography and mass spectrometry. In preliminary investigations, samples were obtained from 2 healthy horses at 12 time points (up to 12 hours after drug administration) and analyzed via 2-stage pharmacokinetic analysis. In the clinical phase, blood samples were obtained from 75 hospitalized horses at various times (total, 2 to 3 samples/horse) up to 9 hours after drug administration, and data were analyzed via a naïve pooled pharmacokinetic model.

Results—In the clinical phase, the apparent terminal half-life (t½) of morphine was approximately 1.5 hours, volume of distribution per bioavailability was approximately 4.5 L/kg, and clearance per bioavailability was approximately 35 mL/kg/min. Peak plasma concentration in naïve pooled analysis was 21.6 ng/mL and occurred approximately 4 minutes after administration. Morphine concentrations were below the limit of quantification ≤ 7 hours after administration in 74 horses. Adverse effects attributed to morphine administration were uncommon and considered mild.

Conclusions and Clinical Relevance—The short t½ of morphine in horses suggested frequent administration may be needed to maintain targeted plasma concentrations. Variations in plasma concentrations suggested optimal dosages may differ among horses. The drug was well tolerated at the described dose, but patients receiving morphine should be monitored carefully.

Full access
in Journal of the American Veterinary Medical Association

Abstract

OBJECTIVE

To assess the pharmacokinetics and opioid effects of methadone after administration of multiple doses by means of 2 dosing regimens of methadone-fluconazole-naltrexone.

ANIMALS

12 healthy Beagles.

PROCEDURES

Dogs were randomly allocated (6 dogs/group) to receive 1 of 2 oral dosing regimens of methadone-fluconazole-naltrexone. Treatment 1 doses were administered at 0 (methadone-to-fluconazole-to-naltrexone ratio of 1:5:0.25 mg/kg), 14 (1:5:0.25), 24 (0.5:2.5:0.125), and 38 (0.5:2.5:0.125) hours. Treatment 2 doses were administered at 0 (1:5:0.25), 4 (0.5:2.5:0.125), 10 (0.5:2.5:0.125), and 24 (0.5:2.5:0.125) hours. Blood samples, rectal temperatures, and von Frey antinociceptive measurements were obtained at designated times.

RESULTS

Compared with baseline, temperatures significantly decreased for treatment 1 group dogs at 2 to ≥ 4 hours and from 16 to ≥ 50 hours (12 hours after last dose) and for treatment 2 group dogs at 2 to ≥ 36 hours (12 hours after last dose), when trough methadone concentrations were ≥ 21.3 ng/mL. Antinociception occurred after the first dose but was not maintained throughout the study. Lesions were noted in some dogs at the application site of the von Frey device. Naltrexone and β-naltrexol were sporadically detected in plasma, and naltrexone glucuronide was consistently detected.

CONCLUSIONS AND CLINICAL RELEVANCE

Opioid effects were noted after oral administration of the first dose, and data suggested that administering a second dose 6 hours later and every 12 hours thereafter was necessary to maintain opioid effects. Antinociception may have been lost because dogs became averse or hyperalgesic to the von Frey device, such that the antinociception model used here may not be robust for repeated measurements in dogs.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To evaluate pharmacokinetics of cefazolin after IV injection of cefazolin (22 mg/kg) and after simultaneous IV and IM injections of cefazolin (total dose, 44 mg/kg) to dogs.

ANIMALS 12 adult Beagles.

PROCEDURES Dogs (6/group) were assigned to receive a single injection of cefazolin (IV group; 22 mg/kg, IV) or simultaneous injections (IV + IM group; 22 mg/kg, IV, and 22 mg/kg, IM). Interstitial fluid was collected over a 5-hour period by use of ultrafiltration probes for pharmacokinetic analysis.

RESULTS Mean cefazolin concentration in the interstitial fluid at 1, 1.5, 2, 3, 4, and 5 hours after injection was 39.6, 29.1, 21.2, 10.3, 6.4, and 2.7 μg/mL, respectively, for the IV group and 38.3, 53.3, 46.4, 31.7, 19.1, and 8.9 μg/mL, respectively, for the IV + IM group. Mean area under the concentration-time curve extrapolated to infinity, maximum concentration, half-life, and time to maximum concentration was 74.99 and 154.16 h·μg/mL, 37.3 and 51.5 μg/mL, 0.96 and 1.11 hours, and 1.28 and 1.65 hours, respectively, for the IV and IV + IM groups.

CONCLUSIONS AND CLINICAL RELEVANCE Cefazolin concentrations in interstitial fluid of dogs were maintained at > 4 μg/mL for 4 hours after a single IV injection and for 5 hours after simultaneous IV and IM injections. Therefore, simultaneous IV and IM administration of cefazolin 30 to 60 minutes before surgery should provide interstitial fluid concentrations effective against the most common commensal organisms (Staphylococcus spp and Streptococcus spp) on the skin of dogs for surgical procedures lasting ≤ 4 hours.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE To determine the effect of oral administration of robenacoxib on inhibition of anterior chamber paracentesis (ACP)-induced breakdown of the blood-aqueous barrier (BAB) and assess whether robenacoxib can cross an intact BAB in healthy cats.

ANIMALS 12 healthy adult domestic shorthair cats.

PROCEDURES Cats received robenacoxib (6-mg tablet in a treat, PO; n = 6) or a control treatment (treat without any drug, PO; 6) once daily for 3 days, beginning 1 day before ACP. One eye of each cat served as an untreated control, whereas the other underwent ACP, during which a 30-gauge needle was used to aspirate 100 μL of aqueous humor for determination of robenacoxib concentration. Both eyes of each cat underwent anterior chamber fluorophotometry at 0 (immediately before), 6, 24, and 48 hours after ACP. Fluorescein concentration and percentage fluorescein increase were used to assess extent of ACP-induced BAB breakdown and compared between cats that did and did not receive robenacoxib.

RESULTS Extent of BAB breakdown induced by ACP did not differ significantly between cats that did and did not receive robenacoxib. Low concentrations of robenacoxib were detected in the aqueous humor (mean, 5.32 ng/mL; range, 0.9 to 16 ng/mL) for 5 of the 6 cats that received the drug.

CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that oral administration of robenacoxib did not significantly decrease extent of BAB breakdown in healthy cats. Detection of low robenacoxib concentrations in the aqueous humor for most treated cats indicated that the drug can cross an intact BAB.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To evaluate the pharmacokinetics and pharmacodynamics of naloxone hydrochloride in dogs following intranasal (IN) and IV administration.

ANIMALS

6 healthy adult mixed-breed dogs.

PROCEDURES

In a blinded crossover design involving 2 experimental periods separated by a washout period (minimum of 7 days), dogs were randomly assigned to receive naloxone IN (4 mg via a commercially available fixed-dose naloxone atomizer; mean ± SD dose, 0.17 ± 0.02 mg/kg) or IV (0.04 mg/kg) in the first period and then the opposite treatment in the second period. Plasma naloxone concentrations, dog behavior, heart rate, and respiratory rate were evaluated for 24 hours/period.

RESULTS

Naloxone administered IN was well absorbed after a short lag time (mean ± SD, 2.3 ± 1.4 minutes). Mean maximum plasma concentration following IN and IV administration was 9.3 ± 2.5 ng/mL and 18.8 ± 3.9 ng/mL, respectively. Mean time to maximum concentration following IN administration was 22.5 ± 8.2 minutes. Mean terminal half-life after IN and IV administration was 47.4 ± 6.7 minutes and 37.0 ± 6.7 minutes, respectively. Mean bioavailability of naloxone administered IN was 32 ± 13%. There were no notable changes in dog behavior, heart rate, or respiratory rate following naloxone administration by either route.

CONCLUSIONS AND CLINICAL RELEVANCE

Use of a naloxone atomizer for IN naloxone administration in dogs may represent an effective alternative to IV administration in emergency situations involving opioid exposure. Future studies are needed to evaluate the efficacy of IN naloxone administration in dogs with opioid intoxication, including a determination of effective doses.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To evaluate the effect of a continuous rate infusion (CRI) of lidocaine on the minimum alveolar concentration (MAC) of isoflurane in rabbits.

Animals—Five 12-month-old female New Zealand White rabbits (Oryctolagus cuniculus).

Procedures—Rabbits were anesthetized with isoflurane. Baseline isoflurane MAC was determined by use of the tail clamp technique. A loading dose of lidocaine (2.0 mg/kg, IV) was administered followed by a CRI of lidocaine at 50 μg/kg/min. After 30 minutes, isoflurane MAC was determined. Another loading dose was administered, and the lidocaine CRI then was increased to 100 μg/kg/min. After 30 minutes, isoflurane MAC was determined again. Plasma samples were obtained for lidocaine analysis after each MAC determination.

Results—Baseline isoflurane MAC was 2.09%, which was similar to previously reported values in this species. Lidocaine CRI at 50 and 100 μg/kg/min induced significant reductions in MAC. The 50 μg/kg/min CRI resulted in a mean plasma lidocaine concentration of 0.654 μg/mL and reduction of MAC by 10.5%. The 100 μg/kg/min CRI of lidocaine resulted in a mean plasma concentration of 1.578 μg/mL and reduction of MAC by 21.7%. Lidocaine also induced significant decreases in arterial blood pressure and heart rate. All cardiopulmonary variables were within reference ranges for rabbits anesthetized with inhalation anesthetics. No adverse effects were detected; all rabbits had an uncomplicated recovery from anesthesia.

Conclusions and Clinical Relevance—Lidocaine administered as a CRI at 50 and 100 μg/kg/min decreased isoflurane MAC in rabbits. The IV administration of lidocaine may be a useful adjunct in anesthesia of rabbits.

Full access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To quantify plasma concentrations of prednisolone and dexamethasone (peripheral and jugular) and cortisol following topical ophthalmic application of 1% prednisolone acetate and 0.1% dexamethasone to healthy adult dogs.

ANIMALS

12 purpose-bred Beagles.

PROCEDURES

Dogs received 1 drop of 1% prednisolone acetate (n = 6) or neomycin polymyxin B dexamethasone (ie, 0.1% dexamethasone; 6) ophthalmic suspension in both eyes every 6 hours for 14 days. Blood samples (peripheral and jugular) were collected on days 0, 1, 7, and 14 and analyzed for plasma prednisolone and dexamethasone concentrations. Plasma cortisol concentrations were measured at the beginning of the study and following topical drug administration.

RESULTS

Both drugs demonstrated systemic absorption. Prednisolone was detected on days 1, 7, and 14 (median plasma concentration, 24.80 ng/mL; range, 6.20 to 74.00 ng/mL), and dexamethasone was detected on days 1, 7, and 14 (2.30 ng/mL; 0 to 17.70 ng/mL). Neither prednisolone nor dexamethasone were detected in plasma samples on day 0 (baseline). Sampling from the jugular vein resulted in higher plasma drug concentrations than from a peripheral vein when samples from each day were combined. Plasma cortisol concentrations were significantly lower than baseline following 14 days of treatment with topical prednisolone acetate and dexamethasone.

CLINICAL RELEVANCE

Prednisolone and dexamethasone are detected in the plasma of healthy dogs following topical ophthalmic administration 4 times/d with prednisolone concentrations being close to a physiologic dose of orally administered prednisolone. Additional research is needed to evaluate the systemic absorption of these medications in dogs with ocular inflammation.

Full access
in American Journal of Veterinary Research

Abstract

Objective—To determine the pharmacokinetic parameters of xylazine, ketamine, and butorphanol (XKB) administered IM and sodium salicylate (SAL) administered PO to calves and to compare drug effects on biomarkers of pain and distress following sham and actual castration and dehorning.

Animals—40 Holstein bull calves from 3 farms.

Procedures—Calves weighing 108 to 235 kg (n = 10 calves/group) received one of the following treatments prior to sham (period 1) and actual (period 2) castration and dehorning: saline (0.9% NaCl) solution IM (placebo); SAL administered PO through drinking water at concentrations from 2.5 to 5 mg/mL from 24 hours prior to period 1 to 48 hours after period 2; butorphanol (0.025 mg/kg), xylazine (0.05 mg/kg), and ketamine (0.1 mg/kg) coadministered IM immediately prior to both periods; and a combination of SAL and XKB (SAL+XKB). Plasma drug concentrations, average daily gain (ADG), chute exit velocity, serum cortisol concentrations, and electrodermal activity were evaluated.

Results—ADG (days 0 to 13) was significantly greater in the SAL and SAL+XKB groups than in the other 2 groups. Calves receiving XKB had reduced chute exit velocity in both periods. Serum cortisol concentrations increased in all groups from period 1 to period 2. However, XKB attenuated the cortisol response for the first hour after castration and dehorning and oral SAL administration reduced the response from 1 to 6 hours. Administration of XKB decreased electrodermal activity scores in both periods.

Conclusions and Clinical Relevance—SAL administered PO through drinking water decreased cortisol concentrations and reduced the decrease in ADG associated with castration and dehorning in calves.

Full access
in American Journal of Veterinary Research