Buprenorphine In Cats Research Articles

The analgesic effects of buprenorphine (Vetergesic or Simbadol) in cats undergoing dental extractions: A randomized, blinded, clinical trial.

This study aimed to evaluate the analgesic efficacy of two dosage regimens using two different concentrations of buprenorphine in cats undergoing dental extractions. Twenty-three cats with oral disease (8.2 ± 2.2 years old; 4.9 ± 0.9 kg) were included in a prospective, blinded, randomized clinical trial. Cats randomly received either Simbadol (1.8 mg/mL; 0.24 mg/kg, subcutaneously, every 24h: SG, n = 11) or Vetergesic (0.3 mg/mL; 0.02 mg/kg, intramuscularly, every 8h: VG, n = 12) throughout the study. They were admitted at day 0, underwent oral examination/radiographs/treatment under general anesthesia (buprenorphine-propofol-isoflurane-meloxicam-local anesthetic blocks) at day 1 and discharged at day 4. Sedation and pain were scored using the dynamic interactive visual analog scale (day 1) and the Glasgow Composite Measure Pain Scale-Feline (CMPS-F; up to postoperative 8 hours at day 1, 8 am, 4 pm and midnight at days 2 and 3, and 8 am at day 4), respectively. Rescue analgesia was administered with hydromorphone (0.05 mg/kg intravenously on day 1 or 0.1 mg/kg intramuscularly after day 2) when CMPS-F ≥ 5. Resentment defined as any type of escape behavior associated with aversion to drug administration was recorded. Sedation and pain scores, the prevalence of rescue analgesia and resentment during drug administration were analyzed using linear mixed models and Fisher’s exact test, respectively (p < 0.05). Pain and sedation scores were not significantly different between groups. Sedation scores were significantly higher up to postoperative 2 hours in both groups. Pain scores in SG and VG were significantly higher up to postoperative 8 hours and 8 am of day 2, respectively, than baseline. Prevalence of rescue analgesia and resentment were not significantly different between groups (SG: 27.3%, VG: 33.3% and SG: 0%, VG: 25%, respectively). Simbadol produced similar analgesic effects to Vetergesic without resentment during drug administration.

Comparison of two high doses of subcutaneous buprenorphine in cats undergoing ovariohysterectomy

Objectives: The aim of the study was to evaluate the analgesia and recovery effects of two doses (0.12 mg/kg and 0.24 mg/kg) of subcutaneous buprenorphine in cats undergoing ovariohysterectomy. Methods: This was an assessor-blinded, randomised, clinical study. A total of 83 cats were recruited and randomly allocated to receive 0.12 mg/kg buprenorphine or 0.24 mg/kg buprenorphine subcutaneously, followed 30 minutes later by 40 μg/kg medetomidine intramuscularly. Anaesthesia was induced with intravenous alfaxalone to effect and maintained with isoflurane in oxygen. All cats received meloxicam before surgery. Temperament score, quality of sedation, induction of anaesthesia, dose of alfaxalone and recovery were scored using simple descriptive scales. Atipamazole was administered following surgery. Physiological variables during anaesthesia were recorded. Cats were assessed postoperatively by the same blinded observer at 2, 4 and 24 hours using a modified Colorado Feline Acute Pain scale. The presence or absence of mydriasis was noted. Results: No significant differences were identified between groups. Three cats in the 0.12 mg/kg group and four in the 0.24 mg/kg group required rescue analgesia. Mydriasis persisting for at least 24 hours was evident in 75 cats. Conclusions and relevance: No differences in analgesia were detected between groups with these protocols; mydriasis was common in both groups.

Analgesic Efficacy of Bupivacaine or Bupivacaine-Dexmedetomidine After Intraperitoneal Administration in Cats: A Randomized, Blinded, Clinical Trial.

The aim of this study was to compare the analgesic efficacy of intraperitoneal bupivacaine vs. bupivacaine-dexmedetomidine in combination with intramuscular buprenorphine in cats undergoing ovariohysterectomy. Sixty healthy adult cats (2.8 ± 0.7 kg; n = 30/group) were included in a randomized, prospective, blinded, clinical trial after owners' written consent. After premedication with acepromazine (0.02 mg/kg) and buprenorphine (0.02 mg/kg) intramuscularly, anesthesia was induced with propofol to effect (6.2 ± 1.4 mg/kg) and maintained with isoflurane. Bupivacaine 0.25% alone (BG; 2 mg/kg) or bupivacaine (same dose) with dexmedetomidine (BDG; 1 μg/kg) were instilled/splashed over the ovarian pedicles and caudal aspect of uterus before ovariohysterectomy. Final injectate volume was standardized between groups. Sedation was evaluated using a five-point simple descriptive scale. Pain was evaluated using the short-form UNESP-Botucatu composite pain scale (SF-CPS) before, and at 0.5, 1, 2, 3, 4, 6, 8, 12, and 24 h after surgery. Rescue analgesia was provided with buprenorphine (0.02 mg/kg intravenously) and meloxicam (0.2 mg/kg subcutaneously) when SF-CPS ≥ 4. The Mantel-Haenszel chi-square test was used for analyzing ordinal variables (e.g., SF-CPS pain scores). The effect of time in SF-CPS scores was assessed with the Cochran-Mantel-Haenszel test for repeated measures. The alpha level for each contrast was adjusted downward with the sequential Benjamini-Hochberg procedure. The number of cats receiving rescue analgesia was analyzed using χ2 test (p < 0.05). The prevalence of rescue analgesia was the same for the two treatments (p = 1.000) [BG, n = 6, 20%; BDG, n = 6, 20%] and similar for timing of rescue analgesia (p = 0.16). The SF-CPS scores were significantly increased between 1 and 12 h in BG, and between 0.5 and 8 h in BDG when compared with baseline values. Median (interquartile range) pain scores were higher in BG [1 (1–2)] than BDG [1 (0–1)] at 12 h (p = 0.023). Sedation scores were not significantly different between groups throughout the study. In terms of prevalence of rescue analgesia, but not duration of action, the analgesic efficacy of bupivacaine-dexmedetomidine was similar to bupivacaine alone after intraperitoneal administration in cats receiving buprenorphine.

Pharmacokinetics of low-dose and high-dose buprenorphine in cats after rectal administration of different formulations.

A prospective experimental study was performed in nine young healthy cats to investigate a pharmacokinetic profile and the clinical relevance of rectally administered buprenorphine. Rectal pH value was measured in all nine cats. Blood was collected 15, 30, 60, 90, 120, 240 and 480 mins and 24 h after the rectal administration of a suppository and a gel at doses between 0.02 mg/kg and 0.1 mg/kg buprenorphine to determine the plasma concentration of buprenorphine. Rectal pH was measured with pH paper. Upon pharmacokinetic non-compartment analysis of high-dose buprenorphine (0.1 mg/kg), average maximal plasma concentration was found to be 1.13 ng/ml, time to maximal plasma concentration was 45 mins and area under the plasma concentration-time curve was 94.19 ng*min/ml, representing low but potential bioavailability. Mean residual time was 152.2 mins and the half-life was 92.6 mins. A wide range of plasma concentrations within the cohort was measured and two of the cats had to be excluded from statistical analysis owing to incomplete uptake. Vital parameters of all cats were considered to be normal but three of the cats showed mydriasis up to 8 h after application. After the administration of a low-dose suppository or a rectal gel (0.02 mg/kg) within pilot studies, no buprenorphine was detected in cat plasma. Rectal pH in all cats was between 7.7 and 8. The rectal application of buprenorphine at a dose of 0.1 mg/kg revealed a potential but weak uptake in cats. Regarding effective concentrations in previous pharmacokinetic investigations, rectal administration is currently not recommended for good provision of opioid analgesia in cats. Pharmacological investigations of formulation and galenics in order to improve the rectal bioavailability of buprenorphine remain to be clarified before further dose-finding and pharmacokinetic/pharmacodynamic studies are performed.

Sciatic and femoral nerve blockade using bupivacaine alone, or in combination with dexmedetomidine or buprenorphine in cats

The aim of this study was to determine the onset and offset of antinociception after sciatic (ScN) and femoral (FN) nerve blocks. Six healthy adult cats (4.8±1.3years; 4.3±0.4 kg) were...

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 0.02mg/kg buprenorphine solution (STD-BUP), followed 14days later by a subcutaneous injection of 0.2mg/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 4.39h average terminal half-life. The subcutaneous SUS-BUP produced plasma buprenorphine concentrations above 0.5μg/L for more than 96h, with three distinct peaks in the first 15h. 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.

Intraoperative end-tidal concentration of isoflurane in cats undergoing ovariectomy that received tramadol, buprenorphine or a combination of both.

Objectives The aim of the study was to evaluate the end-tidal concentration of isoflurane required to maintain heart and respiratory rate within ± 20% of basal measurement in cats undergoing ovariectomy that received buprenorphine, tramadol or a combination of both. Methods Thirty cats, divided into three groups, were enrolled in a simple operator-blinded, randomised study. Cats received acepromazine (0.03 mg/kg) and one of the following treatments: buprenorphine (0.02 mg/kg), tramadol (2 mg/kg) or a combination of both. Anaesthesia was induced with propofol and maintained with isoflurane titrated in order to maintain heart and respiratory rate within the target values recorded before premedication. Results Groups were similar for age, weight, dose of propofol administered, sedation and recovery scores. Cats receiving tramadol with buprenorphine were extubated earlier after isoflurane discontinuation. No statistical differences were detected in end-tidal fraction of isoflurane between buprenorphine alone or with tramadol. In cats that received tramadol or buprenorphine alone, ovarian pedicle traction caused a statistical increase in end-tidal isoflurane concentration compared with that measured during incision and suture of the skin. In cats that received the combination of tramadol plus buprenorphine no differences among surgical time points were observed. Conclusions and relevance Tramadol added to buprenorphine did not provide any advantage in decreasing the end-tidal fraction of isoflurane compared with buprenorphine alone, although it is speculated there may be an infra-additive interaction between tramadol and buprenorphine in cats.

Evaluation of the influence of atipamezole on the postoperative analgesic effect of buprenorphine in cats undergoing a surgical ovariohysterectomy

ObjectiveTo evaluate the influence of atipamezole on postoperative pain scores in cats. Study designControlled, randomized, masked clinical trial. AnimalsTwelve healthy female domestic cats. MethodsCats admitted for ovariohysterectomy (OVH) surgery were randomly allocated to group atipamezole (n = 6) or group saline (n = 6) and were premedicated with buprenorphine 20 μg kg−1 intramuscularly (IM) and alfaxalone 3.0 mg kg−1 subcutaneously (SC). Anaesthesia was induced with alfaxalone intravenously (IV) to effect and maintained with isoflurane in oxygen. Ten minutes after extubation, cats from group atipamezole received IM atipamezole (0.0375 mg kg−1) whereas group saline received an equivalent volume [0.0075 mL kg−1 (0.003 mL kg−1 IM)] of 0.9% saline. A validated multidimensional composite scale was used to assess pain prior to premedication and postoperatively (20 minutes after extubation). If postoperative pain scores dictated, rescue analgesia consisting of buprenorphine and meloxicam were administered. Pain score comparisons were made between the two groups using a Mann–Whitney exact test. Results are reported as the median and range. ResultsPreoperatively, all cats scored 0. At the postoperative pain evaluation, the pain scores from group atipamezole [16 (range, 12–20)] were not significantly different from group saline [18 (range, 15–23)] (p = 0.28). All cats required rescue analgesia post-operatively. Conclusions and clinical relevanceAtipamezole (0.0375 mg kg−1 IM) administration did not significantly affect the postoperative pain scores in cats after OVH. Preoperative administration of buprenorphine (20 μg kg−1 IM) did not provide adequate postoperative analgesia for feline OVH.

Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats.

Plasma concentrations and pharmacokinetics of dexmedetomidine and buprenorphine after oral transmucosal (OTM) and intramuscular (i.m.) administration of their combination in healthy adult cats were compared. According to a crossover protocol (1-month washout), a combination of dexmedetomidine (40μg/kg) and buprenorphine (20μg/kg) was given OTM (buccal cavity) or i.m. (quadriceps muscle) in six female neutered cats. Plasma samples were collected through a jugular catheter during a 24-h period. Plasma dexmedetomidine and buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry. Plasma concentration-time data were fitted to compartmental models. For dexmedetomidine and buprenorphine, the area under the plasma concentration-time curve (AUC) and the maximum plasma concentrations (Cmax ) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach Cmax was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40μg/kg) combined with buprenorphine (20μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.

A review of the studies using buprenorphine in cats.

Pain management is a crucial component of feline medicine and surgery. This review critically evaluates studies using buprenorphine in cats and highlights the clinical application of the opioid in this species. The pharmacokinetic‐pharmacodynamic (PK‐PD) modeling of IV buprenorphine has been best described by a combined effect compartmental/receptor association‐dissociation model with negative hysteresis. Therefore, plasma concentrations of the drug are not correlated with analgesia, and clinicians should not expect to observe pain relief immediately after drug administration. In addition, a ceiling effect has not been demonstrated after administration of clinical doses of buprenorphine in cats; dosages of up to 0.04 mg/kg have been reported. The route of administration influences the onset, duration, and magnitude of antinociception and analgesia when using this drug in cats. At clinical dosages, the SC route of administration does not appear to provide adequate antinociception and analgesia whereas the buccal route has produced inconsistent results. Intravenous or IM administration at a dosage of 0.02–0.04 mg/kg is the preferred for treatment of pain in the acute setting. A literature search found 14 clinical trials evaluating buprenorphine sedation, analgesia, or both in cats. There were 22 original research studies reporting the antinociceptive effects of buprenorphine by means of thermal threshold, mechanical threshold, or both, minimal alveolar concentration, or PK‐PD. Individual variability in response to buprenorphine administration has been reported, indicating that buprenorphine may not provide sufficient analgesia in some cats. Pain assessment is important when evaluating the efficacy of buprenorphine and determining whether additional analgesic treatment is needed.

Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats. Study designRandomized, prospective, blinded, three period crossover experiment. AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg. MethodsBuprenorphine (0.02 mg kg−1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics. ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t1/2ke0 = 47.4 minutes) and receptor binding (kon = 0.011 mL ng−1 minute−1). Persistence of thermal antinociception was due to slow receptor dissociation (t1/2koff = 18.2 minutes). Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.

Combination of dexmedetomidine with buprenorphine enhances the antinociceptive effect to a thermal stimulus in the cat compared with either agent alone

ObjectiveTo evaluate the sedative and antinociceptive effects of combinations of dexmedetomidine and buprenorphine in cats. Study designExperimental randomized study. AnimalsTwelve purpose-bred neutered domestic short-hair cats (4 male and 8 female) weighing 4.6 kg (range 3.7–5.5 kg) aged from 2 to 5 years. MethodsSix cats per group were administered buprenorphine (B) at 10 (B10) or 20 μg kg−1 (B20) or dexmedetomidine (D) at 20 (D20) or 40 μg kg−1 (D40) or a combination of B10/D20. A feline thermal nociceptive threshold testing device was used to evaluate the antinociceptive effects of the drugs before and up to 24 hours after drug treatment. Sedation was scored using a 100 mm visual analogue scale (VAS). ResultsThermal thresholds increased significantly after administration of all but D20. Area under the curve (AUC, hours °C) for the first 6 hours (mean ± SD) for B20 (281 ± 17.8) was significantly greater than B10 (260 ± 11.4), D20 (250 ± 7.9) and D40 (255 ± 11.4). The AUC for B10/D20 (273 ± 12.2) was significantly greater than D20 but not the other treatments. No sedation was seen after administration of B10 or B20 and maximal sedation was seen for all animals in the D40 and B10/D20 groups and most animals in the D20 group. ConclusionsD20 alone had the smallest analgesic effect; B10 alone provided no sedation but their combination gave good sedation with analgesia comparable with B20. Clinical relevanceThis combination could be a useful multimodal sedative/analgesic regimen in cats.

Dose-related antinociceptive effects of intravenous buprenorphine in cats

The dose-related antinociceptive effects of intravenous (IV) buprenorphine were evaluated in cats. Thermal (TT) and mechanical threshold (MT) devices were used for nociceptive stimulation. After baseline threshold recordings, buprenorphine was administered IV (0.01, 0.02 or 0.04 mg/kg; B1, B2 and B4, respectively) in a randomised, blinded and cross-over study. Data were analysed by ANOVA (P<0.05) using 95% confidence intervals (CI). TT increased 15, 30, 45 min and 1 (5.2+/-2.7 degrees C), 2, 3 and 4 h after B1; 15, 30, 45 min and 1 (5.1+/-3.9 degrees C) and 2 h after B2, and 15, 30, 45 min and 1 (5.4+/-3.3 degrees C), 2, 3, 6 and 8 h after B4. MT increased 15 and 45 min after B2 (260+/-171 mmHg), and 30 (209+/-116 mmHg) and 45 min and 1 and 2 h after B4. At 45 min, MT values were significantly higher after B2 compared to B1 (P<0.05). With MT, B2 and B4 produced more antinociception and longer duration of action than B1, respectively. No dose response to thermal stimulation was detected.

Effects of epidurally administered morphine or buprenorphine on the thermal threshold in cats

To determine the antinociceptive effects of epidural administration of morphine or buprenorphine in cats by use of a thermal threshold model. 6 healthy adult cats. Baseline thermal threshold was determined in duplicate. Cats were anesthetized with isoflurane in oxygen. Morphine (100 microg/kg diluted with saline [0.9% NaCl] solution to a total volume of 0.3 mL/kg), buprenorphine (12.5 microg/kg diluted with saline solution to a total volume of 0.3 mL/kg), or saline solution (0.3 mL/kg) was administered into the epidural space according to a Latin square design. Thermal threshold was determined at various times up to 24 hours after epidural injection. Epidural administration of saline solution did not affect thermal threshold. Thermal threshold was significantly higher after epidural administration of morphine and buprenorphine, compared with the effect of saline solution, from 1 to 16 hours and 1 to 10 hours, respectively. Maximum (cutout) temperature was reached without the cat reacting in 0, 74, and 11 occasions in the saline solution, morphine, and buprenorphine groups, respectively. Epidural administration of morphine and buprenorphine induced thermal antinociception in cats. At the doses used in this study, the effect of morphine lasted longer and was more intense than that of buprenorphine.

Use of a transdermal matrix patch of buprenorphine in cats: preliminary pharmacokinetic and pharmacodynamic data

Six domestic shorthair cats, aged three to four years and weighing 5·1 to 7·4 kg, were used to assess the thermal antinociceptive effect of a transdermal buprenorphine patch, designed to...

PK‐PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration1

The pharmacokinetics and thermal antinociceptive effects of buprenorphine after intravenous (i.v.) or oral transmucosal (OTM) administration were studied in six adult cats. Plasma buprenorphine concentrations were measured using radioimmunoassay in a crossover study after a dose of 20 microg/kg given by the i.v. or OTM route. Oral pH was measured. Blood for drug analyses was collected before, and at 1, 2, 4, 6, 10, 15, 30, and 60 min and at 2, 4, 6, 8, 12, and 24 h after treatment. Thermal thresholds were measured before treatment, then following treatment every 30 min to 6 h, every 1 hour to 12 h and at 24 hours postadministration. Plasma buprenorphine concentration effect relationships were analyzed using a log-linear effect model. Oral pH was 9 in each cat. Peak plasma buprenorphine concentration was lower and occurred later in the OTM group but median bioavailability was 116.3%. Thermal thresholds increased significantly between 30 and 360 min in both groups. Peak effect was at 90 min and there was no difference at any time between the two groups. There was distinct hysteresis between plasma drug concentration and effect in both groups. Overall, OTM administration of buprenorphine is as effective as i.v. treatment and offers a simple, noninvasive method of administration which produces thermal antinociception for up to 6 h in cats.