Disposition of levetiracetam in healthy adult horses.

Nine horses received 20 mg/kg of intravenous (LEVIV ); 30 mg/kg of intragastric, crushed immediate release (LEVCIR ); and 30 mg/kg of intragastric, crushed extended release (LEVCER ) levetiracetam, in a three-way randomized crossover design. Crushed tablets were dissolved in water and administered by nasogastric tube. Serum samples were collected over 48 hr, and levetiracetam concentrations were determined by immunoassay. Mean ± SD peak concentrations for LEVCIR and LEVCER were 50.72 ± 10.60 and 53.58 ± 15.94 µg/ml, respectively. The y-intercept for IV administration was 64.54 ± 24.99 µg/ml. The terminal half-life was 6.38 ± 1.97, 7.07 ± 1.93 and 6.22 ± 1.35 hr for LEVCIR , LEVCER, and LEVIV , respectively. Volume of distribution at steady-state was 630 ± 73.4 ml/kg. Total body clearance after IV administration was 74.40 ± 19.20 ml kg-1  hr-1 . Bioavailability was 96 ± 10, and 98 ± 13% for LEVCIR and LEVCER , respectively. A single dose of Levetiracetam (LEV) was well tolerated. Based on this study, a recommended dosing regimen of intravenous or oral LEV of 32 mg/kg every 12 hr is likely to achieve and maintain plasma concentrations within the therapeutic range suggested for humans, with optimal kinetics throughout the dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic studies are warranted.

Pharmacokinetics of Single Oral Dose Extended-Release Levetiracetam in Healthy Cats.

BACKGROUND: Repeated PO dosing of anti-epileptic drugs may contribute to poor compliance in treated cats. Intermediate-release levetiracetam has been used safely in cats, but must be given q8h to maintain serum concentrations in the therapeutic interval for humans (5-45 µg/mL). Approved extended-release levetiracetam (XRL) for human use may require less frequent dosing, but the large dosing unit has limited its use in cats. HYPOTHESES: In healthy cats, serum levetiracetam concentration will remain above 5 µg/mL for at least 24 hours after administration of a single dose of XRL PO and will be well tolerated. ANIMALS: 7 healthy cats. METHODS: Extended-release levetiracetam (500 mg) was administered PO. Blood was collected and neurologic examination findings recorded at scheduled times over 30 hours. Serum levetiracetam concentration was quantitated by an immunoassay validated in cats. Data were subjected to noncompartmental analysis. Descriptive statistics were reported. RESULTS: The median dosage of 86.2 mg/kg, (range, 80-94.3) achieved a mean maximum concentration (Cmax ) of 89.8 ± 25.8 µg/mL at 4.9 ±1.57 hours. Serum levetiracetam was >5 µg/mL in all cats by 90 minutes. Mean concentrations were 43.7 ± 18.4 and 4.9 ± 3.4 µg/mL at 12 and 24 hours, respectively. The half-life was 4.1 ± 1.0 hours. The drug was well tolerated. CONCLUSIONS AND CLINICAL IMPORTANCE: A single 500 mg PO dose of XRL safely maintained serum levetiracetam concentration ≥5 µg/mL in healthy cats for at least 21 hours. Clinical efficacy studies in epileptic cats receiving XRL are indicated; however, monitoring should be implemented for individual cats.

Pharmacokinetics and dynamics of mycophenolate mofetil after single-dose oral administration in juvenile dachshunds.

Mycophenolate mofetil (MMF) is recommended as an alternative/complementary immunosuppressant. Pharmacokinetic and dynamic effects of MMF are unknown in young-aged dogs. We investigated the pharmacokinetics and pharmacodynamics of single oral dose MMF metabolite, mycophenolic acid (MPA), in healthy juvenile dogs purpose-bred for the tripeptidyl peptidase 1 gene (TPP1) mutation. The dogs were heterozygous for the mutation (nonaffected carriers). Six dogs received 13 mg/kg oral MMF and two placebo. Pharmacokinetic parameters derived from plasma MPA were evaluated. Whole-blood mitogen-stimulated T-cell proliferation was determined using a flow cytometric assay. Plasma MPA Cmax (mean ± SD, 9.33 ± 7.04 µg/ml) occurred at <1 hr. The AUC0-∞ (mean ± SD, 12.84±6.62 hr*µg/ml), MRTinf (mean ± SD, 11.09 ± 9.63 min), T1/2 (harmonic mean ± PseudoSD 5.50 ± 3.80 min), and k/d (mean ± SD, 0.002 ± 0.001 1/min). Significant differences could not be detected between % inhibition of proliferating CD5+ T lymphocytes at any time point (p = .380). No relationship was observed between MPA concentration and % inhibition of proliferating CD5+ T lymphocytes (R = .148, p = .324). Pharmacodynamics do not support the use of MMF in juvenile dogs at the administered dose based on existing therapeutic targets.

Disposition of Extended Release Levetiracetam in Normal Healthy Dogs After Single Oral Dosing.

BACKGROUND: Levetiracetam is an anticonvulsant used for control of canine epilepsy. An extended release preparation should improve dosing convenience. OBJECTIVES: To determine the disposition of extended release levetiracetam in normal dogs after single dosing. ANIMALS: Pharmacokinetic study: 16 healthy, adult dogs. METHODS: Using a partially randomized crossover study, levetiracetam (30 mg/kg) was administered intravenously (i.v.) and orally (p.o.) as extended release preparation with or without food. Blood was collected for 24 hours (i.v.) or 36 hours (p.o.). Serum levetiracetam was quantitated by immunoassay and data were subjected to noncompartmental analysis. RESULTS: Pharmacokinetic parameters for fasted versus fed animals, respectively, were (mean ± SEM): Cmax = 26.6 ± 2.38 and 30.7 ± 2.88 µ/mL, Tmax = 204.3 ± 18.9 and 393.8 ± 36.6 minutes, t1/2 = 4.95 ± 0.55 and 4.48 ± 0.48 hours, MRT = 9.8 ± 0.72 and 10 ± 0.64 hours, MAT = 4.7 ± 0.38 and 5.6 ± 0.67 hours, and F = 1.04 ± 0.04 and 1.26 ± 0.07%. Significant differences were limited to Tmax (longer) and F (greater) in fed compared to fasted animals. Serum levetiracetam concentration remained above 5 µ/mL for approximately 20 hours in both fasted and fed animals. CONCLUSIONS AND CLINICAL IMPORTANCE: Extended release levetiracetam (30 mg/kg q12h), with or without food, should maintain concentrations above the recommended minimum human therapeutic concentration.

Oral cyclosporine treatment in dogs: a review of the literature.

Cyclosporine is an immunomodulatory drug used to treat an increasing spectrum of diseases in dogs. Cyclosporine is a calcineurin inhibitor, ultimately exerting its inhibitory effects on T-lymphocytes by decreasing production of cytokines, such as interleukin-2. Although, in the United States, oral cyclosporine is approved in dogs only for treatment of atopic dermatitis, there are many other indications for its use. Cyclosporine is available in 2 oral formulations: the original oil-based formulation and the more commonly used ultramicronized emulsion that facilitates oral absorption. Ultramicronized cyclosporine is available as an approved animal product, and human proprietary and generic preparations are also available. Bioavailability of the different formulations in dogs is likely to vary among the preparations. Cyclosporine is associated with a large number of drug interactions that can also influence blood cyclosporine concentrations. Therapeutic drug monitoring (TDM) can be used to assist in attaining consistent plasma cyclosporine concentrations despite the effects of varying bioavailability and drug interactions. TDM can facilitate therapeutic success by guiding dose adjustments on an individualized basis, and is recommended in cases that do not respond to initial oral dosing, or during treatment of severe, life-threatening diseases for which a trial-and-error approach to dose adjustment is too risky. Pharmacodynamic assays that evaluate individual patient immune responses to cyclosporine can be used to augment information provided by TDM.

Pharmacokinetics of tramadol and its major metabolites in alpacas following intravenous and oral administration.

Tramadol, a centrally acting opioid analgesic with monamine reuptake inhibition, was administered to six alpacas (43-71 kg) randomly assigned to two treatment groups, using an open, single-dose, two-period, randomized cross-over design at a dose of 3.4-4.4 mg/kg intravenously (i.v.) and, after a washout period, 11 mg/kg orally. Serum samples were collected and stored at -80°C until assayed by HPLC. Pharmacokinetic parameters were calculated. The mean half-lives (t(1/2)) i.v. were 0.85±0.463 and 0.520±0.256 h orally. The Cp(0) i.v. was 2467±540 ng/mL, and the C(max) was 1202±1319 ng/mL orally. T(max) occurred at 0.111±0.068 h orally. The area under the curve (AUC(0-∞)) i.v. was 895±189 and 373±217 ng*h/mL orally. The volume of distribution (V(d[area])) i.v. was 5.50±2.66 L/kg. Total body clearance (Cl) i.v. was 4.62±1.09 h; Cl/F for oral administration was 39.5±23 L/h/kg. The i.v. mean residence time (MRT) was 0.720±0.264. Oral adsorption (F) was low (5.9-19.1%) at almost three times the i.v. dosage with a large inter-subject variation. This may be due to binding with the rumen contents or enzymatic destruction. Assuming linear nonsaturable pharmacokinetics and absorption processes, a dosage of 6.7 times orally would be needed to achieve the same i.v. serum concentration of tramadol. The t(1/2) of all three metabolites was longer than the parent drug; however, O-DMT, N-DMT, and Di-DMT metabolites were not detectable in all of the alpacas. Because of the poor bioavailability and adverse effects noted in this study, the oral administration of tramadol in alpacas cannot be recommended without further research.

Antimicrobial resistance profiles and clonal relatedness of canine and feline Escherichia coli pathogens expressing multidrug resistance in the United States.

BACKGROUND: Antimicrobial resistance is increasing among Escherichia coli isolates associated with spontaneous infection in dogs and cats. OBJECTIVES: To describe E. coli resistance phenotypes and clonal relatedness and their regional prevalence. ANIMALS: Isolates of E. coli (n = 376) collected from dogs and cats in the United States between May and September 2005. METHODS: Isolates submitted from the South, West, Northeast, and Midwest regions of the United States were prospectively studied. Phenotype was based on E-test susceptibility to 7 antimicrobials. Isolates were classified as no (NDR), single (SDR), or multidrug resistance (MDR). Clonal relatedness was determined by pulsed-field gel electrophoresis (PFGE). RESULTS: One hundred and ninety-three (51%) isolates expressed resistance to at least 1 drug, yielding 42 phenotypes. SDR isolates (n = 84; 44%, 8 phenotypes), expressed resistance most commonly to amoxicillin (30%, n = 25) and least commonly to cefpodoxime (1%, n = 1). MDR isolates (n = 109; 56%, 31 phenotypes) were resistant to amoxicillin (96%, n = 105), amoxicillin-clavulanate (85%, n = 93), and enrofloxacin (64%, n = 70); 18% (n = 20) were resistant to all drugs tested. The frequency of MDR did not differ regionally (P = .066). MDR minimum inhibitory concentrations (MICs) were 6-fold higher than SDR MICs (P < .0001). Dendrograms of 91 isolates representing 25 phenotypes revealed 62 different PFGE profiles. CONCLUSIONS AND CLINICAL IMPORTANCE: E. coli strains spontaneously infecting dogs and cats are genetically and phenotypically diverse. Given the current prevalence of MDR among clinical isolates of E. coli in United States, implementation of a robust surveillance program is warranted.

Evaluation of the distribution of enrofloxacin by circulating leukocytes to sites of inflammation in dogs.

OBJECTIVE: To determine the effect of WBC accumulation on the concentration of enrofloxacin in inflamed tissues in dogs. ANIMALS: 6 adult Bloodhounds. PROCEDURES: Dogs were instrumented bilaterally with tissue chambers. Peripheral WBCs collected from each dog were exposed in vitro to radiolabeled enrofloxacin ((14)C-ENR). Inflammation was induced with carrageenan in 1 chamber. Ten hours later, treated cells were administered IV to each dog such that (14)C-ENR was delivered at a mean +/- SD dosage of 212 +/- 43 microg. Samples of extracellular fluid from inflammation and control chambers and circulating blood were then collected before (baseline) and for 24 hours after WBCs were administered. Samples were centrifuged to separate WBCs from plasma (blood) or chamber fluid. Radiolabeled enrofloxacin was scintigraphically detected and pharmacokinetically analyzed. Comparisons were made between extra- and intracellular chamber fluids by use of a Student paired t test. RESULTS: (14)C-ENR was not detectable in plasma, peripheral WBCs, control chambers, or baseline samples from inflammation chambers. However, (14)C-ENR was detected in extra- cellular fluid from inflammation chambers (mean +/- SD maximum concentration, 2.3 +/- 0.5 ng/mL) and WBCs (maximum concentration, 7.7 +/- 1.9 ng/mL). Mean disappearance half-life of (14)C-ENR from extracellular fluid and WBCs from inflammation chambers was 26 +/- 10 hours and 17 +/- 6 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: WBCs were responsible for the transport and release of (14)C-ENR at sites of inflammation. Accumulation of drug by WBCs might increase the concentration of drug at the site of infection, thus facilitating therapeutic success.

Disposition and safety of zonisamide after intravenous and oral single dose and oral multiple dosing in normal hound dogs.

The purpose of this study was to determine an oral dosing regimen of zonisamide in healthy dogs such that therapeutic concentrations would be safely reached and maintained at steady-state. Adult hound dogs (n = 8) received a single IV (6.9) and an oral (PO) dose (10.3 mg/kg) using a randomized cross-over design. Zonisamide was then administered at 10.3 mg/kg PO every 12 h for 8 weeks. Zonisamide was quantitated in blood compartments or urine by HPLC and data were subjected to noncompartmental pharmacokinetic analysis. Comparisons were made among blood compartments (one-way anova; P

Pharmacokinetics and pharmacodynamics of butorphanol in llamas after intravenous and intramuscular administration.

OBJECTIVE: To evaluate disposition of butorphanol after i.v. and i.m. administration, effects on physiologic variables, and analgesic efficacy after i.m. administration in llamas. DESIGN: Nonrandomized crossover study. ANIMALS: 6 healthy adult male llamas. PROCEDURE: Butorphanol (0.1 mg/kg [0.045 mg/lb] of body weight) was administered i.m. first and i.v. 1 month later. Blood samples were collected intermittently for 24 hours after administration. Plasma butorphanol versus time curves were subjected to pharmacokinetic analysis. Two months later, butorphanol (0.1 mg/kg) was administered i.m., and physiologic variables and analgesia were assessed. RESULTS: Extrapolated peak plasma concentrations after i.v. and i.m. administration were 94.8 +/- 53.1 and 34.3 +/- 11.6 ng/ml, respectively. Volume of distribution at steady state after i.v. administration was 0.822 +/- 0.329 L/kg per minute and systemic clearance was 0.050 +/- 0.014 L/kg per minute. Slope of the elimination phase was significantly different, and elimination half-life was significantly shorter after i.v. (15.9 +/- 9.1 minutes) versus i.m. (66.8 +/- 13.5 minutes) administration. Bioavailability was 110 +/- 49% after i.m. administration. Heart rate decreased and rectal temperature increased. Somatic analgesia was increased for various periods. Two llamas became transiently sedated, and 2 became transiently excited after butorphanol administration. CONCLUSIONS AND CLINICAL RELEVANCE: Although i.v. administration of butorphanol results in a short half-life that may limit its analgesic usefulness, the elimination half-life of butorphanol administered i.m. is likely to be clinically useful. The relationship among plasma butorphanol concentration, time, and analgesia differed with the somatic analgesia model; clinically useful analgesia may occur at lower plasma concentrations than those reported here.

Hyperactivity and alopecia associated with ingestion of valproic acid in a cat.

A 1-year-old castrated male cat was evaluated because of alopecia of approximately 4 to 5 months' duration as well as hyperactive behavior. It was later determined that the cat was ingesting valproic acid by eating food to which it had been added for daily administration to a child in the household who had cerebral palsy. The clinical signs slowly resolved after the source of valproic acid was removed. This emphasizes the sensitivity of cats to drugs that are commonly used in humans. It was not determined whether the clinical signs that developed in this cat were caused by an adverse reaction or from toxicosis as a result of prolonged hepatic elimination of valproic acid, which requires glucuronide metabolism for disposition. However, the cat recovered completely following removal of the drug and prevention of further exposure. This report emphasizes the importance of obtaining a careful and complete history from the owner regarding an animal and its environment. In the cat of this report, the owner had not considered the impact of the presence of the drug in the child's food.

Tissue concentrations of enrofloxacin and ciprofloxacin in anesthetized dogs following single intravenous administration.

Concentrations of enrofloxacin and its active metabolite, ciprofloxacin, were detected in tissues following single intravenous administration of 20 mg/kg to four anesthetized dogs. Two hours after treatment, serum samples were collected, animals were euthanized, and tissues were collected from each dog. Solid tissues were homogenized, and both enrofloxacin and ciprofloxacin were detected using high-performance liquid chromatography. Enrofloxacin was detected in all tissues examined; the highest concentrations were found in the gall bladder, urine, bile, stomach, and liver. Concentrations in the cerebral cortex, cerebrospinal fluid, skin, and prostate were 5.7, 5.3, 9.2, and 23.5 microg/ml, respectively. Tissues for which the concentration of enrofloxacin was 4 microg/ml or lower included the trachea, articular cartilage, aqueous humor, fat, and tendon. An inhibitory quotient of 8 or more was achieved for enrofloxacin in the majority of tissues studied. Ciprofloxacin was detected in 29 of 40 tissues examined.

Evaluation of transdermal fentanyl patches for analgesia in cats undergoing onychectomy.

OBJECTIVE: To evaluate efficacy and safety of using transdermal fentanyl patches (TFP) for analgesia in cats undergoing onychectomy. DESIGN: Randomized controlled clinical trial. ANIMALS: 45 client-owned cats weighing > or = 2.7 kg (5.9 lb) undergoing onychectomy, onychectomy and ovariohysterectomy, or onychectomy and castration. PROCEDURE: Cats were randomly assigned to be treated with a TFP (25 micrograms/h) or butorphanol; TFP were applied a minimum of 4 hours before surgery (approx 8 hours prior to extubation). Rectal temperature, heart rate, respiratory rate, force applied by the forelimbs, and serum fentanyl concentration were measured, and temperament, recovery, degree of sedation, severity of pain, severity of lameness, and appetite were scored before and periodically for up to 40 hours after surgery. RESULTS: Cats treated with a TFP had better recovery scores at 2 of 4 evaluation times, lower sedation scores at 2 of 8 evaluation times, and lower pain scores at 6 of 8 evaluation times, compared with cats treated with butorphanol. Use of a pressure-sensitive mat to evaluate force applied by the forelimbs did not reveal any differences between groups but did reveal a significant difference between preoperative and postoperative values. Mean +/- SD serum fentanyl concentrations were 1.56 +/- 1.08, 4.85 +/- 2.38, 4.87 +/- 1.56, and 4.35 +/- 2.97 ng/ml approximately 8, 24, 32, and 48 hours, respectively, after TFP placement. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of a TFP (25 micrograms/h) for postoperative analgesia in cats undergoing onychectomy with or without surgical sterilization is safe and effective.

Nitric oxide generation in a rat model of acute portal hypertension.

OBJECTIVE: To document blood nitric oxide concentrations in the portal vein and systemic circulation in a rat model of acute portal hypertension and compare values with a control group and a sham surgical group. ANIMALS: 30 rats; 10 controls (group 1), 10 sham surgical (group 2), and 10 rats with surgically induced acute portal hypertension (group 3). PROCEDURE: Following induction of anesthesia, catheters were placed surgically in the carotid artery, jugular, and portal veins of group 2 and 3 rats and in the carotid artery and jugular vein of group 1 rats. Baseline heart and respiratory rates, rectal temperature, and vascular pressure measurements were obtained, and blood was drawn from all catheters for baseline nitric oxide (NO) concentrations. Acute portal hypertension was induced in the group 3 rats by tying a partially occluding suture around the portal vein and a 22-gauge catheter. The catheter was then removed, resulting in a repeatable degree of portal vein impingement. After catheter placement, all variables were remeasured at 15-minute intervals for 3 hours. RESULTS: Blood nitric oxide concentrations were greater in all vessels tested in group 3 than in group 2 rats. CONCLUSIONS AND CLINICAL RELEVANCE: Acute portal hypertension in this experimental model results in increased concentrations of NO in the systemic and portal circulation. On the basis of information in the rat, it is possible that increased NO concentrations may develop in dogs following surgical treatment of congenital portosystemic shunts if acute life-threatening portal hypertension develops. Increased NO concentrations may contribute to the shock syndrome that develops in these dogs.

Comparison of nuclear scintigraphy and acetaminophen absorption as a means of studying gastric emptying in horses.

OBJECTIVE: To evaluate the correlation between halftime of liquid-phase gastric emptying (T50), determined with nuclear scintigraphy using technetium Tc 99m pentetate, and absorption variables of orally administered acetaminophen. ANIMALS: 6 mature horses. PROCEDURE: Technetium Tc 99m pentetate (10 mCi) and acetaminophen (20 mg/kg of body weight) were administered simultaneously in 200 ml of water. Serial left and right lateral images of the stomach region were obtained with a gamma camera, and T50 determined separately for counts obtained from the left side, the right side and the geometric mean. Power exponential curves were used for estimation of T50 and modified R2 values for estimation of goodness of fit of the data. Serial serum samples were taken, and acetaminophen concentration was determined, using fluorescence polarization immunoassay. Maximum serum concentration (Cmax), time to reach maximum serum concentration (Tmax), area under the curve for 240 minutes and the absorption constant (Ka) were determined, using a parameter estimation program. Correlations were calculated, using the Spearman rank correlation coefficient. RESULTS: Correlations between T50 and Tmax and between T50 and Ka were significant. CONCLUSIONS AND CLINICAL RELEVANCE: Tmax and Ka are valuable variables in the assessment of liquid-phase gastric emptying using acetaminophen absorption. Acetaminophen absorption may be a valuable alternative to nuclear scintigraphy in the determination of gastric emptying rates in equine patients with normally functioning small intestine.

A canine model of multiple portosystemic shunting.

The objective of this study was to develop and describe an experimental canine model of multiple acquired portosystemic shunts (PSS) similar in nature to spontaneously occurring PSS. Sixteen dogs were used and were divided into a control (n = 6) and a diseased group (n = 10). Dogs of the diseased group were administered dimethylnitrosamine (2 mg/kg of body weight, po) twice weekly, and clinicopathologic, ultrasonographic, and hepatic scintigraphic findings were recorded during the development of hepatic disease and PSS. Surgery was then performed to permit visual verification of multiple shunts, catheter placement for portography examination, and biopsy of the liver. All diseased dogs developed severe hepatic disease and multiple PSS as documented visually at surgery and on portography. Based on this study, dimethylnitrosamine-induced portosystemic shunting appears to be an appropriate model for spontaneously occurring multiple PSS secondary to portal hypertension.

Drugs affecting the respiratory system.

Differences in the disposition of drugs among exotic animals is a well-recognized hurdle when treating disease. Differences exist in pharmacokinetics, pharmacodynamics, and disease processes. This article focuses on the principles of treating respiratory tract diseases, with the recognition that not all drugs are indicated for use in all exotic species. The discussion begins with a description of respiratory physiology as it pertains to response to drugs, using the mammalian lung as a template. The role of respiratory defense mechanisms in airway protection and disease is addressed. Drugs used to treat the respiratory tract include the bronchodilators and anti-inflammatory drugs, drugs that modify respiratory secretions (e.g., mucolytics, mucokinetics, and expectorants), antitussive drugs, and decongestants. Aerosolization is an important adjuvant for respiratory therapy as long as precautions are met. Infectious diseases are among the more common respiratory diseases encountered, and the discussion includes a focus on the use of antibiotics for treating respiratory tract infections.

Pharmacokinetics of fentanyl after intravenous and transdermal administration in goats.

OBJECTIVE: To evaluate disposition of fentanyl in goats after IV and transdermal administration. ANIMALS: 8 healthy 2-year-old goats weighing 31.8 to 53.6 kg (mean+/-SD, 40.4+/-7.5 kg). PROCEDURE: Each goat was given 2 treatments consisting of fentanyl administered IV (2.5 microg/kg of body weight) and via a transdermal patch (50 microg/h). There was a 2-month interval between treatments. Blood samples were collected at specified times and analyzed in duplicate to determine plasma fentanyl concentrations. Pharmacokinetic values were calculated, using a computerized modeling program. RESULTS: Administration of fentanyl was tolerated by all goats. Intravenous administration of fentanyl resulted in a transitory increase in rectal temperature that was not clinically important. Terminal elimination half-life after IV administration was 1.20+/-0.78 h, volume of distribution at steady state was 1.51+/-0.39 L/kg, and systemic clearance was 2.09+/-0.62 L/kg/h. Transdermal administration of fentanyl resulted in variable plasma concentrations, with peak plasma concentrations ranging from 1.12 to 16.69 ng/ml (mean+/-SD, 6.99+/-6.03 ng/ml) and time to peak concentration ranging from 8 to 18 hours (mean+/-SD, 13+/-4.5 hours). After removal of the transdermal patch, mean+/-SD terminal elimination half-life was 5.34+/-5.34 hours. CONCLUSIONS AND CLINICAL RELEVANCE: Intravenous administration of fentanyl (2.5 microg/kg) in goats results in a relatively short half-life that will limit its use for management of pain. Transdermal administration of fentanyl (50 microg/h) in goats results in variable plasma concentrations that may exceed those anticipated on the basis of a theoretical delivery rate, but stable plasma concentrations of fentanyl may not be achieved.