Development and validation of a sleep questionnaire, SNoRE 3.0, to evaluate sleep in companion dogs.

Disturbances in the sleep-wake cycle are a debilitating, yet rather common condition not only in humans, but also in family dogs. While there is an emerging need for easy-to-use tools to document sleep alterations (in order to ultimately treat and/or prevent them), the veterinary tools which yield objective data (e.g. polysomnography, activity monitors) are both labor intensive and expensive. In this study, we developed a modified version of a previously used sleep questionnaire (SNoRE) and determined criterion validity in companion dogs against polysomnography and physical activity monitors (PAMs). Since a negative correlation between sleep time and cognitive performance in senior dogs has been demonstrated, we evaluated the correlation between the SNoRE scores and the Canine Dementia Scale (CADES, which includes a factor concerning sleep). There was a significant correlation between SNoRE 3.0 questionnaire scores and polysomnography data (latency to NREM sleep, ρ = 0.507, p < 0.001) as well as PAMs' data (activity between 1:00 and 3:00 AM, p < 0.05). There was a moderate positive correlation between the SNoRE 3.0 scores and the CADES scores (ρ = 0.625, p < 0.001). Additionally, the questionnaire structure was validated by a confirmatory factor analysis, and it also showed an adequate test-retest reliability. In conclusion the present paper describes a valid and reliable questionnaire tool, that can be used as a cost-effective way to monitor dog sleep in clinical settings.

Identification of canine osteoarthritis using an owner-reported questionnaire and treatment monitoring using functional mobility tests.

OBJECTIVES: To investigate the diagnostic value of an owner-completed canine osteoarthritis screening checklist to help identify previously undiagnosed osteoarthritis cases, and assess their response to carprofen treatment by monitoring pain and functional mobility. MATERIALS AND METHODS: Dogs (n=500) whose owners reported ≥1 positive response to the osteoarthritis checklist were examined to identify dogs with previously undiagnosed osteoarthritis. Eligible dogs (n=133) were evaluated for pain and video mobility analysis by Helsinki Chronic Pain Index and visual analogue scale scores, respectively, following carprofen treatment, administered for 30 days (n=95) or up to 120 days (n=38). Dogs were filmed at clinics performing activities (walking, jogging, sitting/lying, walking up and down stairs), and scored at days 0, 30 and 120 using visual analogue scale by an independent blinded expert. RESULTS: A diagnosis of osteoarthritis was confirmed by a veterinarian in 38% (188 of 500) of dogs. Balance of sensitivity and specificity across the original group of nine screening questions was optimised to approximately 88 and 71%, respectively, after elimination of three questions. Pain measured by Helsinki Chronic Pain Index and functional mobility improved over time in response to treatment with carprofen. Mean ability scores for activities significantly improved between days 0 and 30 for walking, jogging, sitting/lying and walking down stairs, and days 0 and 120 for sitting/lying and walking up stairs. CLINICAL SIGNIFICANCE: More osteoarthritis cases were identified in study dogs than previous prevalence estimates, indicating the screening checklist's potential to help identify for further evaluation cases that could otherwise remain undiagnosed. Improvements in function were demonstrated after carprofen treatment.

Atenolol in cats with subclinical hypertrophic cardiomyopathy: a double-blind, placebo-controlled, randomized clinical trial of effect on quality of life, activity, and cardiac biomarkers.

OBJECTIVE: To compare quality of life (QOL) and activity measures between healthy control cats and cats with subclinical hypertrophic cardiomyopathy (HCM), and to evaluate the effect of oral atenolol therapy on QOL, activity, and circulating biomarkers in cats with subclinical HCM. ANIMALS: Thirty-two client-owned cats with subclinical HCM and 27 healthy control cats. METHODS: Owner responses to a QOL questionnaire, circulating cardiac biomarker concentrations, and accelerometer-based activity measures were compared prospectively in cats with and without HCM, and in cats with HCM before and after treatment with oral atenolol (6.25 mg/cat q 12 h) for 6 months. RESULTS: Owner-assessed activity of daily living score was lower in cats with HCM than in cats in controls (p=0.0420). No differences were identified between control cats and cats with HCM for any activity variable. Compared with placebo, treatment with atenolol was associated with a lower baseline-adjusted mean ± SD heart rate (157 ± 30 vs. 195 ± 20 bpm; p=0.0001) and rate-pressure product (22,446 ± 6,237 vs. 26,615 ± 4,623 mmHg/min; p=0.0146). A treatment effect of atenolol on QOL or activity was not demonstrated. CONCLUSIONS: This study failed to identify an effect of subclinical HCM on owner-assessed QOL or activity or a treatment effect of atenolol on these variables at the dosage evaluated. These findings do not support a treatment benefit of atenolol for the goal of symptom reduction in cats with subclinical HCM.

Placebo-controlled pilot study of the effects of an eggshell membrane-based supplement on mobility and serum biomarkers in dogs with osteoarthritis.

Osteoarthritis (OA) is a debilitating disease in dogs. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat OA; however, many dogs do not obtain adequate pain relief with an NSAID alone. This pilot study evaluated the systemic anti-inflammatory and mobility enhancing effects of an eggshell membrane-based nutritional supplement in dogs with OA-associated pain and mobility impairment. Twenty-seven dogs with OA-associated pain were enrolled into a randomized, double-masked, placebo-controlled, proof of principle pilot study and received either placebo or an eggshell membrane-based nutritional supplement over a 12-week period. Inflammatory biomarkers (IL-2, IL-6, IL-8, tumor necrosis factor-α, C-reactive protein, S100A12, and N-methylhistamine) were measured at Day 0 and Day 84. Owner questionnaires (CBPI and LOAD) were completed at Day 0, Day 42, and Day 84. Differences between groups over time were calculated. Twenty-two dogs completed the pilot study. Inflammatory biomarker IL-2 decreased in the supplement group, compared to the placebo group. Although small, the difference was statistically significant at an alpha of 0.1 (P=0.069). LOAD scores were numerically lower in the supplement group, but not significantly different from the placebo group at Day 0. Day 84 LOAD scores were significantly lower in the supplement group compared to the placebo group (P=0.034). CBPI results did not show the same pattern. The changes in biomarkers and LOAD scores were small, and do not provide definitive evidence of positive effects. However, these pilot results provide a rationale for performing a larger placebo-controlled study of the potential effects of the eggshell membrane-based nutritional supplement.

Functional linear modeling of activity data shows analgesic-mediated improved sleep in dogs with spontaneous osteoarthritis pain.

In humans, pain due to osteoarthritis has been demonstrated to be associated with insomnia and sleep disturbances that affect perception of pain, productivity, and quality of life. Dogs, which develop spontaneous osteoarthritis and represent an increasingly used model for human osteoarthritis, would be expected to show similar sleep disturbances. Further, these sleep disturbances should be mitigated by analgesic therapy. Previous efforts to quantify sleep in osteoarthritic dogs using accelerometry have not demonstrated a beneficial effect of analgesic therapy; this is despite owner-reported improvements in dogs' sleep quality. However, analytic techniques for time-series accelerometry data have advanced with the development of functional linear modeling. Our aim was to apply functional linear modeling to accelerometry data from osteoarthritic dogs participating in a cross-over non-steroidal anti-inflammatory (meloxicam) drug trial. Significant differences in activity patterns were seen dogs receiving drug (meloxicam) vs. placebo, suggestive of improved nighttime resting (sleep) and increased daytime activity. These results align with owner-reported outcome assessments of sleep quality and further support dogs as an important translational model with benefits for both veterinary and human health.

Measurement of chronic pain in companion animals: Priorities for future research and development based on discussions from the Pain in Animals Workshop (PAW) 2017.

The estimation of long-standing pain in companion animals through the measurement of different dimensions impacted by pain is a fundamental requirement if pain management, and pain therapeutic development, are to advance. Although pain management in veterinary medicine has advanced considerably in the last 20 years, there is much critical work to do in the area of measurement of chronic pain. To date, most work has centered on musculoskeletal pain, and has been focused around the measurement of limb use and the development of owner-completed questionnaires, or clinical metrology instruments (CMI). Recent areas of research have extended to developing measures of activity, sensory function (quantitative sensory testing; nociceptive withdrawal reflexes), and quality of life (QoL). Across all these areas, more data on validity are needed, and studies should be extended to other painful disease states. By necessity, assessing measurement tools requires testing in field studies, which incur considerable time and expense. Facilitating these studies could be optimized with a collaborative (industry, academia and private practice) approach, and the utility of the information produced from all field studies would be enhanced by full and transparent reporting and data sharing, including data already generated by industry in the form of studies submitted to the regulatory authorities.

Measurement of chronic pain in companion animals: Discussions from the Pain in Animals Workshop (PAW) 2017.

In the face of increasing recognition and interest in treating chronic pain in companion animals, we struggle with a lack of therapeutic options. A significant barrier to the development of new therapeutics, or the critical evaluation of current therapies, is our inability to accurately measure chronic pain and its impact on companion animals. Over the last 20 years, much progress has been made in developing methods to measure chronic pain via subjective and objective methods - particularly in owner assessment tools and measurements of limb use and activity. Most work has been focused on chronic joint pain conditions, but there has been relatively little work in other areas of chronic pain, such as neuropathic and cancer pain. Although progress has been made, there is a considerable interest in improving our assessment of chronic pain, as evidenced by the multiple disciplines across industry, academia, and clinical practice from the veterinary and human medical fields that participated in the Pain in Animals Workshop held at the National Institutes of Health in 2017. This review is one product of that meeting and summarizes the current state of knowledge surrounding the measurement of chronic pain (musculoskeletal, cancer, neuropathic), and its impact, in cats and dogs.

Long-term use of non-steroidal anti-inflammatory drugs in cats with chronic kidney disease: from controversy to optimism.

This is the first of a series of capsule reviews published by the World Small Animal Veterinary Association - Global Pain Council (WSAVA-GPC). Each of these short articles provides a brisk assessment of the scientific evidence in specific aspects of pain management, including analgesic techniques, recommendations and controversies surrounding their use. In this first capsule review, the scientific evidence available on the long-term use of non-steroidal anti-inflammatory drugs in cats with concomitant chronic pain and chronic kidney disease is discussed.

Characterization of gene expression in naturally occurring feline degenerative joint disease-associated pain.

Degenerative joint disease (DJD) associated-pain is a clinically relevant and common condition affecting domesticated cats and other species including humans. Identification of the neurobiological signature of pain is well developed in rodent pain models, however such information is lacking from animals or humans with naturally occurring painful conditions. In this study, identification of housekeeping genes (HKG) for neuronal tissue and expression levels of genes considered associated with chronic pain in rodent models were explored in cats with naturally occurring osteoarthritic pain. Fourteen adult cats were evaluated - seven without clinical signs of osteoarthritic pain, and seven with hind limb radiographic DJD and pain. Expression of an investigator-selected set of pain signaling genes (including ASIC3, ATF3, COX2, CX3CL1, NAV1.7, NAV1.8, NAV1.9, NGF, NK1R, TNFα, TRKA) in lumbar spinal cord dorsal horn and lumbar dorsal root ganglia tissues from clinically healthy cats and cats with DJD were studied using quantitative RT-PCR (qPCR). HKG identified as the most stable across all tissue samples were many of the ribosomal protein genes, such as RPL30 and RPS19. qPCR results showed ATF3 and CX3CL1 up-regulated in DJD-affected dorsal root ganglia compared to clinically healthy controls. In spinal cord, CX3CL1 was up-regulated and NGF was down-regulated when DJD-affected samples were compared to healthy samples. Further work is needed to understand the neurobiology of pain in naturally occurring disease and what rodent models are predictive of these changes in more heterogeneous populations such as domestic cats.

Evaluation of the effect of signalment and owner-reported impairment level on accelerometer-measured changes in activity in osteoarthritic dogs receiving a non-steroidal anti-inflammatory.

In veterinary medicine, evaluation of osteoarthritis (OA) treatment efficacy remains challenging. Measurement of activity, utilizing accelerometers, provides a surrogate measure of pain through measuring effects on activity, and the objective data collected can be used to assess the efficacy of treatments. However, little is known about how dog characteristics impact the accelerometry-measured response to treatment. The objectives of this study were to evaluate the effect of signalment and initial impairment level on accelerometer-measured changes in activity in osteoarthritic dogs after receiving a non-steroidal anti-inflammatory (NSAID). Fifty-seven client-owned dogs with OA-associated pain and mobility impairment were administered meloxicam for 2 weeks, following a 2-week baseline, and spontaneous activity was measured using an Actical accelerometer unit. Signalment factors and disease variables were recorded (age, sex, weight, impairment level, forelimb or hindlimb pain). Initial degree of impairment had a significant effect on changes in weekly (P=0.009), weekday (P=0.044) activity following NSAID treatment. Greater initial impairment was associated with larger positive changes in activity. Degree of impairment should be taken into consideration during the development of a clinical trial. Appropriate selection of candidates based on initial degree of impairment may permit a greater treatment effect, therefore increasing the power of the study.

Initial evaluation of PetPace activity monitor.

Mobility is considered a vital component of health and quality of life in humans and companion animals. Wearable devices for pets that can monitor activity and other aspects of health are increasingly being marketed to veterinarians and owners, with claims around their ability to monitor aspects of health. However, there is little scientific evidence to support the validity of these claims. To address this, the objective of this study was to assess the correlation of the activity measurement from the PetPace device compared to activity output from Actigraph and the validated Actical device. Ten client-owned, healthy dogs were used for the study. The three devices were mounted simultaneously on a dedicated collar and activity was recorded during a period of 7 days. There were moderate correlations between the Actical and the PetPace (r2=0.59, P=<0.001). There was high correlation between the PetPace and the Actigraph (r2=0.85, P=<0.001) and between the Actical and the Actigraph (r2=0.72, P=<0.001). If the Actical activity counts were limited under 50,000 per hour, there was strong correlation between the Actical and the PetPace (r2=0.71, P=<0.001) and between the Actical and the Actigraph (r2=0.86, P=<0.001). PetPace has a moderate correlation with the most validated activity monitor that has been used in veterinary medicine. Its real-time data acquisition, user friendly interface for owners and cost make this device an attractive tool for monitoring activity in dogs. Further studies maybe needed to evaluate its performance, validity and clinical utility in the field.

Influence of gait on bone strength in turkeys with leg defects.

Leg problems have become more frequent in fast-growing turkeys. The objective of this study was to evaluate the effects of common leg defects on kinetic parameters of gait and biomechanical properties of bone. Nine hundred, day-old, male, Large White turkeys were raised in 48 floor pens. At 42 d of age, turkeys were divided into four categories of leg condition as determined by visual evaluation: Normal, Crooked toes, Shaky legs, and Valgus. Fifteen toms were selected from each group and trained to walk on a pressure sensitive walkway. Gait kinetic data were collected at 92, 115 and 144 d of age. At 145 d of age, turkeys were sacrificed and bones were collected and frozen until analysis. Morphological measurements of femur, tibia and tarsus-metatarsus were recorded. Bone mineral density (BMD) and content (BMC) were obtained using DEXA. Bone strength of tibias was evaluated using a four-point bending test and femurs with a torsion test. ANOVA was used to detect differences among groups, and Tukey's test used for mean separation. There were no differences in BW among different leg conditions. Gait parameters changed as turkeys aged, and age-group interactions were observed on peak vertical force (PVF), contact time, step length (SL) and bipedal cycle. No differences (P > 0.05) were detected in morphological measurements of femur or tibia. Relative asymmetry of femur length was lower (P < 0.05) in Normal and Valgus turkeys than in toms with Crooked toes. There were no differences (P > 0.05) among groups for femur BMD, BMC or strength. Tibia BMD and the area moment of inertia of turkeys with Crooked toes were lower (P < 0.05) than in toms with Valgus. With all four leg conditions, femur strength was positively correlated with PVF and negatively correlated with SL; BMD and BMC were correlated with tibia strength and gait kinetic parameters. In conclusion, only crooked toes caused consistent differences in gait patterns, bone properties and bone strength, but in general, gait kinetics was correlated with bone biomechanics in turkeys.

The pharmacokinetics and analgesic effects of extended-release buprenorphine administered subcutaneously in healthy dogs.

Buprenorphine is a partial µ agonist opioid used for analgesia in dogs. An extended-release formulation (ER-buprenorphine) has been shown to provide effective analgesia for 72 hr in rats and mice. Six healthy mongrel dogs were enrolled in a randomized, blinded crossover design to describe and compare the pharmacokinetics and pharmacodynamics of ER-buprenorphine administered subcutaneous at 0.2 mg/kg (ER-B) and commercially available buprenorphine for injection intravenously at 0.02 mg/kg (IV-B). After drug administration, serial blood samples were collected to measure plasma buprenorphine concentrations using liquid chromatography/mass spectrometry detection. Heart rate, respiratory rate, body temperature, sedation score, and thermal threshold latency were recorded throughout the study. Median (range) terminal half-life, time to maximum concentration, and maximum plasma concentration of ER-buprenorphine were 12.74 hr (10.43-18.84 hr), 8 hr (4-36 hr), and 5.00 ng/ml (4.29-10.98 ng/ml), respectively. Mild bradycardia, hypothermia, and inappetence were noted in both groups. Thermal threshold latency was significantly prolonged compared to baseline up to 12 hr and up to 72 hr in IV-B and ER-B, respectively. These results showed that ER-buprenorphine administered at a dose of 0.2 mg/kg resulted in prolonged and sustained plasma concentrations and antinociceptive effects up to 72 hr after drug administration.

Spontaneous painful disease in companion animals can facilitate the development of chronic pain therapies for humans.

OBJECTIVE: To outline the role that spontaneous osteoarthritis (OA) in companion animals can play in translational research and therapeutic pharmacological development. OUTLINE: Narrative review summarizing the opportunities and limitations of naturally occurring, spontaneous OA as models of human OA pain, with a focus on companion animal pets. The background leading to considering inserting spontaneous disease models in the translational paradigm is provided. The utility of this model is discussed in terms of outcome measures that have been validated as being related to pain, and in terms of the potential for target discovery is outlined. The limitations to using companion animal pets as models of human disease are discussed. CONCLUSIONS: Although many steps along the translational drug development pathway have been identified as needing improvement, spontaneous painful OA in companion animals offers translational potential. Such 'models' may better reflect the complex genetic, environmental, temporal and physiological influences present in humans and current data suggests the predictive validity of the models are good. The opportunity for target discovery exists but is, as yet, unproven.

Questionnaire-based Analysis of Owner-reported Scratching and Pain Signs in Cavalier King Charles Spaniels Screened for Chiari-like Malformation and Syringomyelia.

BACKGROUND: Chiari-like malformation (CM) and syringomyelia (SM) cause a pain syndrome in Cavalier King Charles spaniels (CKCS). Clinical signs are not consistently apparent on neurologic examination, and owner reporting of signs provides vital clinical history. However, owner questionnaires for this disease are not well developed. OBJECTIVES: To develop a tool to capture owner-reported clinical signs for use in clinical trials and to compare owner-reported signs with the presence of pain on neurologic examination and SM on magnetic resonance imaging (MRI). ANIMALS: Fifty client-owned CKCS. METHODS: Owners completed a questionnaire and pain/scratch map. Each dog underwent a neurologic examination and craniocervical magnetic resonance imaging (MRI). Questionnaire responses were developed into scores, area of shading for pain/scratch maps was measured, and consistency of responses between these tools was assessed. Owner-reported findings were compared with neurologic examination findings and presence and severity of SM on MRI. RESULTS: Thirty-three dogs were symptomatic and 17 asymptomatic; 30 had SM. The most common sign of pain was crying out when lifted (n = 11). Extent of shaded areas on maps positively correlated with questionnaire scores for pain (r2  = 0.213, P = 0.006) and scratch (r2  = 0.104, P = 0.089). Owner-reported findings were not significantly associated with presence or severity of SM or neurologic examination findings. Owner-reported lateralization of signs was significantly associated with SM lateralization (P < 0.0001). CONCLUSIONS: The questionnaire and maps may be useful for clinical trials. Lack of association of owner-reported signs with SM highlights our lack of understanding of the pathophysiology of pain in this disease.

Caregiver placebo effect in analgesic clinical trials for cats with naturally occurring degenerative joint disease-associated pain.

A literature review identified six placebo-controlled studies of analgesics in client-owned cats with degenerative joint disease-associated pain. Five studies with 96 cats had available data. Caregiver responses on a clinical metrology instrument, Client-Specific Outcome Measure (CSOM), were compared to measured activity. Cats were categorised as 'successes' or 'failures' based on change in CSOM score and activity counts from baseline. Effect sizes based on CSOM score were calculated; factors that were associated with success/failure were analysed using logistic regression. Effect sizes ranged from 0.97 to 1.93. The caregiver placebo effect was high, with 54-74 per cent of placebo-treated cats classified as CSOM successes compared with 10-63 per cent of cats classified as successes based on objectively measured activity. 36 per cent of CSOM successes were also activity successes, while 19 per cent of CSOM failures were activity successes. No significant effects of cat age, weight, baseline activity, radiographic score, orthopaedic pain score or study type on CSOM success in the placebo groups were found. The caregiver placebo effect across these clinical trials was remarkably high, making demonstration of efficacy for an analgesic above a placebo difficult. Further work is needed to determine whether a potential placebo-by-proxy effect could benefit cats in clinical settings.

Gait parameters in four strains of turkeys and correlations with bone strength.

Locomotion problems in meat poultry have multifactorial etiology. A better understanding of normal gait and its influences on biomechanical aspects of leg bones among turkey genetic lines is important to prevent skeletal disorders and locomotion issues. The objective of this experiment was to determine the possible differences in gait kinetic and kinematic parameters of turkey strains and their effects on bone biomechanical properties. Four genetic lines, named A, B, C, and D, were obtained and raised in 48 floor pens with new pine shavings. Leg health issues were classified at 16 and 33 d of age. Fifteen turkeys from each strain with apparent normal legs and gait at 33 d of age were selected for gait analysis. These 15 turkeys were trained to walk on a pressure sensitive walkway and video was recorded to calculate articulation movements. These data also were analyzed to obtain kinetic and kinematic parameters of the gait cycle collected at 47, 84, 107, and 145 d of age. At 20 wk all turkeys were sacrificed, and legs were collected and frozen for analysis. Weights and morphologic measurements of the femur, tibia, and shank were recorded. Bone mineral density (BMD) and content (BMC) were obtained using DEXA. Femur and tibia strength were evaluated by a 4-point bending test and torsion test, respectively. Gait parameters changed as toms aged and some differences were observed among lines. Genetic lines differed on BMD, but not on BMC. Strain D had a higher BMD and smaller diaphyseal angle than strain C, characteristics that were correlated with stronger bones. Strain D also had the lowest incidence of leg problems while strain C had the highest. Furthermore, the D strain had a smaller vertical motion of the toe than strains C and B at 47 d and strain A at 145 d, indicating that the D strain had a more efficient gait. In summary, genetic strains differ significantly on gait parameters, which in turn impacts bone biomechanics.

Severity of Nasal Inflammatory Disease Questionnaire for Canine Idiopathic Rhinitis Control: Instrument Development and Initial Validity Evidence.

BACKGROUND: Effective treatments are needed for idiopathic chronic rhinitis in dogs, but assessment of efficacy requires a practical, quantifiable method for assessing severity of disease. OBJECTIVES: To develop and perform initial validity and reliability testing of an owner-completed questionnaire for assessing clinical signs and dog and owner quality of life (QOL) in canine chronic rhinitis. ANIMALS: Twenty-two dogs with histopathologically confirmed chronic rhinitis and 72 healthy dogs. METHODS: In this prospective study, an online questionnaire was created based on literature review and feedback from veterinarians, veterinary internists with respiratory expertise, and owners of dogs with rhinitis. Owners of affected dogs completed the questionnaire twice, 1 week apart, to test reliability. Healthy dogs were assessed once. Data were analyzed using the Rasch Rating Scale Model, and results were interpreted using Messick's framework for evaluating construct validity evidence. RESULTS: Initial item generation resulted in 5 domains: nasal signs, paranasal signs, global rhinitis severity, and dog's and owner's QOL. A 25-item questionnaire was developed using 5-point Likert-type scales. No respondent found the questionnaire difficult to complete. Strong psychometric evidence was available to support the substantive, generalizability, content, and structural aspects of construct validity. Statistical differences were found between responses for affected and control dogs for all but 2 items. These items were eliminated, resulting in the 23-item Severity of Nasal Inflammatory Disease (SNIFLD) questionnaire. CONCLUSIONS AND CLINICAL IMPORTANCE: The SNIFLD questionnaire provides a mechanism for repeated assessments of disease severity in dogs with chronic rhinitis.

Pharmacokinetics of liposomal encapsulated buprenorphine suspension following subcutaneous administration to cats.

We investigated the effects of liposome encapsulation at prolonging the systemic exposure of buprenorphine following subcutaneous administration in cats. Seven healthy male cats were dosed intravenously with 0.02 mg/kg buprenorphine solution (STD-BUP), followed 14 days later by a subcutaneous injection of 0.2 mg/kg buprenorphine as a liposomal suspension (SUS-BUP) containing drug molecules both in liposomes and the suspending vehicle. Buprenorphine time plasma concentration data for both dosing routes were analyzed simultaneously with four compartmental models. Goodness of fit was assessed both graphically and with the Akaike information criterion. The time-course of intravenous STD-BUP was biphasic, with a 4.39 h average terminal half-life. The subcutaneous SUS-BUP produced plasma buprenorphine concentrations above 0.5 µg/L for more than 96 h, with three distinct peaks in the first 15 h. The model with best fit comprised a central and a peripheral compartment, plus three subcutaneous absorption compartments: one of dissolved drug molecules that were absorbed through a first-order process, and two of liposome-encapsulated drug molecules that were transferred to the solution compartment through separate zero-order processes. Liposomes effectively prolonged the systemic exposure of buprenorphine in cats.