Development of a novel immobilisation protocol for black-faced impala (Aepyceros melampus ssp. petersi) in Etosha National Park.

Black-faced impala (Aepyceros melampus ssp. petersi) are endemic to Namibia where conservation management involves immobilisation and translocation, and mortality with current protocols is common. Critically evaluated field immobilisation protocols are needed to maximise animal safety. This prospective study was done in two phases: the first compared etorphine- and thiafentanil-based combinations, the second evaluated the influence of oxygen in impala receiving the thiafentanil-based combination. Animals (10 per group) received 50 mg ketamine (K) and 10 mg butorphanol (B), with either 2.0 mg etorphine (E) or 2.0 mg thiafentanil (T). A third group of ten impala were anaesthetised using TKB with supplemental nasal oxygen (O) at a rate of 5 L/minute. Behavioural, metabolic and physiological variables were assessed within five minutes of recumbency and at 10, 15, and 20 minutes post-recumbency. Statistical analyses for non-parametric data were performed to compare the treatment groups as well as time points; p ≤ 0.05 considered significant. Following darting, 7/10 EKB animals were standing when approached, compared to 2/20 in the thiafentanil treatment groups. Time to first effect was significantly higher for EKB (155 ± 105.7 seconds) compared to TKBO (61.5 ± 21.4 seconds). Time to sternal after darting was significantly higher with EKB (411.6 ± 174 seconds) compared to TKB (160.5 ± 85.4 seconds) and TKBO (166 ± 77.3 seconds). This study builds on previous work investigating the effects of potent opioids on impala and is the first evaluating their use in a field setting. The thiafentanil combination had a faster onset and resulted in a smoother induction than the etorphine combination. Additionally, oxygenation improved in animals receiving oxygen supplementation.

Transvenous occlusion of patent ductus arteriosus in a domestic chicken (Gallus gallus).

A 2.5-year-old intact female Marans domestic chicken was presented for lethargy, open beak breathing, and hyporexia. Echocardiography noted left atrial and left ventricular enlargement and computed tomography angiography revealed a type III left-sided patent ductus arteriosus. Retrograde catheterization of the ductus was performed via percutaneous access of the right external jugular vein, and transvenous ductal occlusion was achieved using an 8-mm Amplatzer™ Vascular Plug 4. Transient bradycardia and hypotension occurred during right heart catheterization, which were successfully treated with atropine and epinephrine. A two-week follow-up postoperative cardiac computed tomography scan confirmed appropriate placement of the occluder within the ductus, and echocardiography demonstrated reduced left heart size. The chicken showed an improvement in clinical signs and remains apparently well six months after the intervention. This report describes the computed tomographic findings of a patent ductus arteriosus in an avian species, minimally invasive transvenous closure of this congenital anomaly with a low-profile occlusion device, and the associated challenges and considerations specific to cardiac intervention in an avian patient.

Plasma and synovial fluid concentrations and cartilage toxicity of bupivacaine following intra-articular administration of a liposomal formulation to horses.

BACKGROUND: The use of intra-articular (IA) local anaesthetics has proven to be an effective means to treat post-operative pain. The effects of local anaesthetics on equine chondrocytes are mixed with some studies reporting chondrodestruction and others no adverse effects. A liposomal formulation of bupivacaine is used in people and dogs by intra- and peri-articular administration to provide up to 72 h of analgesia. The potential uses, side effects including chondrotoxicity, and likelihood of abuse (long-term analgesic effects) has not been evaluated in horses. OBJECTIVES: Describe bupivacaine concentrations following IA administration and assess biomarkers as indicators of the effects of liposomal bupivacaine on chondrocytes in vivo. STUDY DESIGN: Parallel design. METHODS: Sixteen exercised horses received a single IA administration of 0.12 mg/kg liposomal bupivacaine or 0.9% saline. Blood and urine samples were collected for 96 h post-drug administration. Six horses treated with bupivacaine and those receiving saline, underwent daily arthrocentesis. Six additional bupivacaine treated horses underwent arthrocentesis at 96 h. Drug concentrations were measured using LC-MS/MS and pharmacokinetic analyses performed. Immunoassays were used to measure markers of collagen degradation (C2C, C12C) and cartilage matrix synthesis (CPII, CS846) in synovial fluid. RESULTS: The bupivacaine plasma elimination half-life was 17.8 ± 5.42 and 11.9 ± 5.17 h for horses from which synovial fluid was collected daily and at 96 h respectively. Bupivacaine concentrations in the joint were still detectable at 96 h. Significant increases in C12C and C2C were noted at 96 h in horses undergoing arthrocentesis at 96 h only. CPII was increased at 48 h and CS846 at 24 and 48 h in horses sampled daily. MAIN LIMITATIONS: Limited number of animals and absence of liposome control group. CONCLUSIONS: Sustained concentrations of IA bupivacaine suggest viability of this medication as an intra-articular analgesic. Effects on equine chondrocytes need further study.

Single- and multiple dose pharmacokinetics and multiple dose pharmacodynamics of oral ABT-116 (a TRPV1 antagonist) in dogs.

Six dogs were used to determine single and multiple oral dose pharmacokinetics of ABT-116. Blood was collected for subsequent analysis prior to and at 15, 30 min and 1, 2, 4, 6, 12, 18, and 24 h after administration of a single 30 mg/kg dose of ABT-116. Results showed a half-life of 6.9 h, k(el) of 0.1/h, AUC of 56.5 µg·h/mL, T(max) of 3.7 h, and C(max) of 3.8 µg/mL. Based on data from this initial phase, a dose of 10 mg/kg of ABT-116 (no placebo control) was selected and administered to the same six dogs once daily for five consecutive days. Behavioral observations, heart rate, respiratory rate, temperature, thermal and mechanical (proximal and distal limb) nociceptive thresholds, and blood collection were performed prior to and 4, 8, and 16 h after drug administration each day. The majority of plasma concentrations were above the efficacious concentration (0.23 µg/mL previously determined for rodents) for analgesia during the 24-h sampling period. Thermal and distal limb mechanical thresholds were increased at 4 and 8 h, and at 4, 8, and 16 h respectively, postdosing. Body temperature increased on the first day of dosing. Results suggest adequate exposure and antinociceptive effects of 10 mg/kg ABT-116 following oral delivery in dogs.

Pharmacokinetics and pharmacodynamics of intravenous dexmedetomidine in the horse.

The aim of the study was to describe the pharmacokinetics and selected pharmacodynamics of intravenous dexmedetomidine in horses. Eight adult horses received 5 µg/kg dexmedetomidine IV. Blood samples were collected before and for 10 h after drug administration to determine dexmedetomidine plasma concentrations. Pharmacokinetic parameters were calculated using noncompartmental analysis. Data from one outlier were excluded from the statistical summary. Behavioral and physiological responses were recorded before and for 6 h after dexmedetomidine administration. Dexmedetomidine concentrations decreased rapidly (elimination half-life of 8.03 ± 0.84 min). Time of last detection varied from 30 to 60 min. Bradycardia was noted at 4 and 10 min after drug administration (26 ± 8 and 29 ± 8 beats/min respectively). Head height decreased by 70% at 4 and 10 min and gradually returned to baseline. Ability to ambulate was decreased for 60 min following drug administration, and mechanical nociceptive threshold was increased during 30 min. Blood glucose peaked at 30 min (134 ± 24 mg/dL) and borborygmi were decreased for the first hour after dexmedetomidine administration. Dexmedetomidine was quickly eliminated as indicated by the rapid decrease in plasma concentrations. Physiological, behavioral, and analgesic effects observed after dexmedetomidine administration were of short duration.

Pharmacokinetic and pharmacodynamic analysis comparing diverse effects of detomidine, medetomidine, and dexmedetomidine in the horse: a population analysis.

The present study characterizes the pharmacokinetic (PK) and pharmacodynamic (PD) relationships of the α2-adrenergic receptor agonists detomidine (DET), medetomidine (MED) and dexmedetomidine (DEX) in parallel groups of horses from in vivo data after single bolus doses. Head height (HH), heart rate (HR), and blood glucose concentrations were measured over 6 h. Compartmental PK and minimal physiologically based PK (mPBPK) models were applied and incorporated into basic and extended indirect response models (IRM). Population PK/PD analysis was conducted using the Monolix software implementing the stochastic approximation expectation maximization algorithm. Marked reductions in HH and HR were found. The drug concentrations required to obtain inhibition at half-maximal effect (IC50 ) were approximately four times larger for DET than MED and DEX for both HH and HR. These effects were not gender dependent. Medetomidine had a greater influence on the increase in glucose concentration than DEX. The developed models demonstrate the use of mechanistic and mPBPK/PD models for the analysis of clinically obtainable in vivo data.

Pharmacokinetic profile in relation to anaesthesia characteristics after a 5% micellar microemulsion of propofol in the horse.

BACKGROUND: To define the pharmacokinetic profile of propofol 5% microemulsion formulation in horses. METHODS: First, propofol was administered as bolus injection (2 mg kg(-1)) to six xylazine-sedated horses. Secondly, after sedation and bolus injection, propofol was maintained with continuous infusion for 3 h [8.1 (sd 3.2) mg kg(-1) h(-1)] to the same six horses. Thirdly, in two horses, a commercial propofol was used for comparison. Response to noxious stimulation was used to evaluate analgesia. Venous blood samples were obtained to measure propofol plasma concentration using liquid chromatography-mass spectrometry analysis. The plasma concentrations were related to the anaesthesia characteristics to determine the ED(50). RESULTS: The pharmacokinetic profile of propofol is best characterized by a non-compartmental model. The mean (confidence interval) for area under plasma concentration-time curve, elimination half-life, mean residence time, and clearance was 41 min microg ml(-1) (+/-7.7), 44.8 min (+/-21.3), 13.7 min (+/-3.2), and 45.8 ml min(-1) kg(-1) (+/-6.5), respectively. Linear regression analysis showed a correlation between plasma concentration and infusion rate (r(2)=0.47). Most propofol infusion rates did not inhibit the response to noxious stimulation and rates above 11.9 mg kg(-1) h(-1) caused involuntary muscle contractions. Better recoveries were associated with lower propofol plasma concentrations. Propofol plasma concentration frequently increased when horses woke from anaesthesia. CONCLUSIONS: Caution is warranted when propofol is used for continuous infusion due to variable kinetics, myoclonal activity, poor analgesia, and less desirable recovery quality.

Pharmacokinetics of detomidine and its metabolites following intravenous and intramuscular administration in horses.

REASONS FOR PERFORMING STUDY: Detomidine is commonly used i.v. for sedation and analgesia in horses, but the pharmacokinetics and metabolism of this drug have not been well described. OBJECTIVES: To describe the pharmacokinetics of detomidine and its metabolites, 3-hydroxy-detomidine (OH-detomidine) and detomidine 3-carboxylic acid (COOH-detomidine), after i.v. and i.m. administration of a single dose to horses. METHODS: Eight horses were used in a balanced crossover design study. In Phase 1, 4 horses received a single dose of i.v. detomidine, administered 30 microg/kg bwt and 4 a single dose i.m. 30 microg/kg bwt. In Phase 2, treatments were reversed. Plasma detomidine, OH-detomidine and COOH-detomidine were measured at predetermined time points using liquid chromatography-mass spectrometry. RESULTS: Following i.v. administration, detomidine was distributed rapidly and eliminated with a half-life (t1/2(el)) of approximately 30 min. Following i.m. administration, detomidine was distributed and eliminated with t1/2(el) of approximately one hour. Following, i.v. administration, detomidine clearance had a mean, median and range of 12.41, 11.66 and 10.10-18.37 ml/min/kg bwt, respectively. Detomidine had a volume of distribution with the mean, median and range for i.v. administration of 470, 478 and 215-687 ml/kg bwt, respectively. OH-detomidine was detected sooner than COOH-detomidine; however, COOH-detomidine had a much greater area under the curve. CONCLUSIONS AND POTENTIAL RELEVANCE: These pharmacokinetic parameters provide information necessary for determination of peak plasma concentrations and clearance of detomidine in mature horses. The results suggest that, when a longer duration of plasma concentration is warranted, the i.m. route should be considered.

Plasma concentrations, behavioural and physiological effects following intravenous and intramuscular detomidine in horses.

REASONS FOR PERFORMING STUDY: Detomidine hydrochloride is used to provide sedation, muscle relaxation and analgesia in horses, but a lack of information pertaining to plasma concentration has limited the ability to correlate drug concentration with effect. OBJECTIVES: To build on previous information and assess detomidine for i.v. and i.m. use in horses by simultaneously assessing plasma drug concentrations, physiological parameters and behavioural characteristics. HYPOTHESIS: Systemic effects would be seen following i.m. and i.v. detomidine administration and these effects would be positively correlated with plasma drug concentrations. METHODS: Behavioural (e.g. head position) and physiological (e.g. heart rate) responses were recorded at fixed time points from 4 min to 24 h after i.m. or i.v. detomidine (30 microg/kg bwt) administration to 8 horses. Route of administration was assigned using a balanced crossover design. Blood was sampled at predetermined time points from 0.5 min to 48 h post administration for subsequent detomidine concentration measurements using liquid chromatography-mass spectrometry. Data were summarised as mean +/- s.d. for subsequent analysis of variance for repeated measures. RESULTS: Plasma detomidine concentration peaked earlier (1.5 min vs. 1.5 h) and was significantly higher (105.4 +/- 71.6 ng/ml vs. 6.9 +/- 1.4 ng/ml) after i.v. vs. i.m. administration. Physiological and behavioural changes were of a greater magnitude and observed at earlier time points for i.v. vs. i.m. groups. For example, head position decreased from an average of 116 cm in both groups to a low value 35 +/- 23 cm from the ground 10 min following i.v. detomidine and to 64 +/- 24 cm 60 min after i.m. detomidine. Changes in heart rate followed a similar pattern; low value of 17 beats/min 10 min after i.v. administration and 29 beats/min 30 min after i.m. administration. CONCLUSIONS: Plasma drug concentration and measured effects were correlated positively and varied with route of administration following a single dose of detomidine. POTENTIAL RELEVANCE: Results support a significant influence of route of administration on desirable and undesirable drug effects that influence case management.

Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses.

REASONS FOR PERFORMING STUDY: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. OBJECTIVES: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. METHODS: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry. RESULTS: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.

The effects of i.v. fentanyl administration on the minimum alveolar concentration of isoflurane in horses.

BACKGROUND: Fentanyl decreases the minimum alveolar concentration (MAC) of inhaled anaesthetics and has been used clinically to reduce the requirements of other anaesthetic drugs in humans and small animals. We hypothesized that i.v. fentanyl would decrease the MAC of isoflurane in horses in a dose-dependent manner. METHODS: Following determination of baseline MAC of isoflurane, fentanyl was administered i.v. to target plasma concentrations of 1, 8 and 16 ng ml(-1). Each horse was randomly assigned two of three target concentrations administered in ascending order. Loading and infusion doses for each horse were determined from previously derived individual pharmacokinetic values. Isoflurane MAC determination began 45 min after fentanyl administration at each target fentanyl concentration. Venous blood was collected at fixed intervals during the infusion for measurement of plasma fentanyl concentrations. RESULTS: Mean actual fentanyl plasma concentrations were 0 (baseline), and 0.72 (SD 0.26), 8.43 (3.22), and 13.31 (6.66) ng ml(-1) for the target concentrations of 1, 8 and 16 ng ml(-1), respectively. The corresponding isoflurane MAC values were a baseline of 1.57 (0.23), and 1.51 (0.24), 1.41 (0.23) and 1.37 (0.09)%, respectively. The fentanyl concentrations of 0.72 and 8.43 ng ml(-1) did not significantly alter the MAC of isoflurane, but an 18 (7)% ISO-MAC reduction was observed at the 13.31 ng ml(-1) concentration. CONCLUSIONS: These results cautiously encourage further study of fentanyl as an opioid anaesthetic adjunct to inhalant anaesthesia in horses.

Evaluation of opioid receptors in synovial membranes of horses.

OBJECTIVE: To evaluate mu-opioid receptors in synovial membranes of horses and determine whether these receptors are up-regulated in nerve endings during inflammation. SAMPLE POPULATION: Synovial tissue obtained from 39 client-owned horses during arthroscopy and 14 research horses during necropsy; brain and synovial tissues were obtained during necropsy from 1 horse, and control tissues were obtained from a mouse. PROCEDURE: Horses were classified into 7 groups on the basis of histologically determined degree of inflammation. Binding of primary rabbit antibody developed against mu-opioid receptors in equine synovial tissue was studied, using western blot analysis. Synovial membranes were tested for mu-opioid receptors by immunohistochemical staining, using a diaminobenzidine-cobalt chloride chromogen. Homogenates of synovial membranes were evaluated by use of radioligand binding. RESULTS: Examination of western blots of equine thalamus revealed that rabbit antibody developed against mu-opioid receptors yielded a band (molecular weight, 55 kd) that corresponded with that of other opioid receptors. Use of immunohistochemical staining of synovial tissue revealed considerable staining in the proliferative lining layer and in regions surrounding vascular structures. Specific radioligand binding of tissue homogenates was found in all groups. We did not detect significant differences in binding between horses with inflammation and horses without inflammation. CONCLUSIONS AND CLINICAL RELEVANCE: Results of immunohistochemical analysis and radioligand binding of tissue homogenates suggest that there are opioid receptors in synovial membranes of horses. Our results support the practice of intra-articular administration of opioids to relieve pain after arthroscopic surgery in horses.

Analysis of aqueous humor obtained from normal eyes of llamas and alpacas.

OBJECTIVE: To evaluate composition of aqueous humor obtained from normal eyes of llamas (Lama glama) and alpacas (Lama pacos). SAMPLE POPULATION: Aqueous humor obtained from 10 male llamas and 10 male alpacas. PROCEDURE: All animals had normal eyes, as determined by ocular examination. Aqueous humor samples were obtained via paracentesis of the anterior chamber of animals that were heavily sedated. Chemical analysis included measurement of concentrations of sodium, potassium, magnesium, chloride, bicarbonate, phosphorus, and glucose as well as osmolality and pH. RESULTS: With the exception of potassium concentrations, values for aqueous humor composition did not differ significantly between llamas and alpacas. Mean +/- SD values for llamas and alpacas, respectively, were: sodium, 154.7 +/- 2.1 and 152.7 +/- 2.1 mEq/L; potassium, 5.3 +/- 0.4 and 4.6 +/- 0.4 mEq/L; magnesium, 1.8 +/- 0.1 and 1.7 +/- 0.1 mg/dl; chloride, 130.0 +/- 1.6 and 127.0 +/- 3.3 mEq/L; bicarbonate, 19.2 +/- 1.5 and 20.2 +/- 2.3 mEq/L; phosphorous, 2.7 +/- 0.3 and 2.5 +/- 0.4 mg/dl; glucose, 80.3 +/- 3.9 and 80.8 +/- 7.3 mg/dl; total protein, 29.0 +/- 8.6 and 31.5 +/- 10.1 mg/dl; and osmolality, 305.8 +/- 11.8 and 306.2 +/- 4.9 mOsm. The pH ranged from 7.5 to 8.0 for both species. Potassium concentrations were significantly higher in llamas than alpacas. CONCLUSIONS AND CLINICAL RELEVANCE: Except for potassium, composition of aqueous humor did not differ significantly between llamas and alpacas. Aqueous humor composition of llamas and alpacas is similar to that of other species that have been examined.

Effects of diazepam and flumazenil on minimum alveolar concentrations for dogs anesthetized with isoflurane or a combination of isoflurane and fentanyl.

OBJECTIVE: To determine the effect of a constant-rate infusion of fentanyl on minimum alveolar concentration (MAC) of isoflurane and to determine the interaction between fentanyl and a benzodiazepine agonist (diazepam) and antagonist (flumazenil) in isoflurane-anesthetized dogs. ANIMALS: 8 mixed-breed adult dogs. PROCEDURE: Dogs were anesthetized with isoflurane 3 times during a 6-week period. After a 30-minute equilibration period, each MAC determination was performed in triplicate, using standard techniques. Fentanyl was administered as a bolus (10 microg/kg of body weight, IV) that was followed by a constant infusion (0.3 microg/kg per min, IV) throughout the remainder of the experiment. After determining isoflurane-fentanyl MAC in triplicate, each dog received saline (0.9% NaCl) solution, diazepam, or flumazenil. After 30 minutes, MAC was determined again. RESULTS: Fentanyl significantly decreased isoflurane MAC (corrected to a barometric pressure of 760 mm Hg) from 1.80+/-0.21 to 0.85+/-0.14%, a reduction of 53%. Isoflurane-fentanyl-diazepam MAC (0.48+/-0.29%) was significantly less than isoflurane-fentanyl-saline MAC (0.79+/-0.21%). Percentage reduction in isoflurane MAC was significantly greater for fentanyl-diazepam (74%), compared with fentanyl-saline (54%) or fentanyl-flumazenil (61%). Mean fentanyl concentrations for the entire experiment were increased over time and were higher in the diazepam group than the saline or flumazenil groups. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl markedly decreased isoflurane MAC in dogs. Diazepam, but not flumazenil, further decreased isoflurane-fentanyl MAC. Our results indicate that diazepam enhances, whereas flumazenil does not affect, opioid-induced CNS depression and, possibly, analgesia in dogs.

Use of orally administered carfentanil prior to isoflurane-induced anesthesia in a Kodiak brown bear.

A captive 590-kg (1,298-lb) 22-year-old castrated male Kodiak brown bear was evaluated because of a soft tissue mass in the right carpal and antebrachial regions. General anesthesia was deemed necessary on 3 occasions for various procedures including radiographic evaluation and biopsy, excision, and radiation treatment. The bear was given carfentanil orally to induce sedation, followed by i.m. administration of tiletamine-zolazepam (on 1 occasion) and atropine. Anesthesia was maintained by administration of isoflurane in oxygen. After each procedure, effects of carfentanil were reversed by administration of naltrexone. Although there was some variability, blood pressure, nasal temperature, heart rate, respiratory rate, oxygen saturation, PO2, and PCO2 remained within a clinically acceptable ranges.

Pharmacokinetics and cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys (Macaca mulatta).

OBJECTIVE: To determine pharmacokinetics and selected cardiopulmonary effects of fentanyl in isoflurane-anesthetized rhesus monkeys. ANIMALS: 6 adult male rhesus monkeys. PROCEDURE: Fentanyl (8 mg/kg of body weight, IV) was administered to 6 monkeys anesthetized with isoflurane. End-tidal isoflurane concentration and esophageal temperature were kept constant, and ventilation was mechanically assisted. Heart rate, rhythm, aortic blood pressure, and blood pH, gas, and fentanyl concentrations were determined before and for 8 hours after administration of fentanyl. Pharmacokinetics of fentanyl were derived by use of noncompartmental methods based on statistical moment theory. RESULTS: Heart rate and mean arterial pressure decreased transiently following fentanyl administration. Maximal decreases were observed 5 to 15 minutes after administration. Arterial pH, Paco2, and Pao2 ranged from 7.46 +/- 0.04 to 751 +/- 0.05 units, 29.2 +/- 3 to 34.6 +/- 4.4 mm Hg, and 412.6 +/- 105.3 to 482.9 +/- 71.2 mm Hg, respectively. The clearance, volume of distribution area, volume of distribution steady state, mean residence time, area under the curve, elimination rate constant, and half-life were 32.5 +/- 2.48 ml/kg/min, 9.04 +/- 1.91 L/kg, 70 +/- 1.2 L/kg, 218.5 +/- 35.5 min, 0.247 +/- 0.019 mg/ml/min, 0.004 + 0.001/min, and 192.0 +/- 33.5 min, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Transient but potentially clinically important decreases in heart rate and mean arterial pressure were observed following fentanyl administration. Distribution and clearance data were similar to those reported for dogs and humans.