Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats,and effects on thermal threshold

This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration‐thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two‐ and three‐compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady‐state (L/kg), clearance (mL·min/kg), and terminal half‐life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half‐life was 23.7 ± 9.1 min, and terminal half‐life was 8.9 ± 4.9 h. An effect‐compartment model with a simple effect maximum model best predicted the time‐course of the effect of buprenorphine on thermal threshold. Median (range) k_e0 and EC50 were 0.003 (0.002–0.018)/min and 0.599 (0.073–1.628) ng/mL (i.v.), and 0.017 (0.002–0.023)/min and 0.429 (0.144–0.556) ng/mL (buccal).     

The safety of high‐dose buprenorphine administered subcutaneously in cats

The safety of a proprietary formulation of buprenorphine hydrochloride administered subcutaneously (SC) to young cats was investigated in a blinded, randomized study. Four cohorts of eight cats aged approximately 4 months were administered saline, 0.24, 0.72 or 1.20 mg/kg/day buprenorphine SC for nine consecutive days, representing 0×, 1×, 3× and 5× of the intended dose. Cats were monitored daily for evidence of clinical reactions, food and water intake and adverse events (AEs). Physical examinations, clinical pathology, vital signs and electrocardiograms (ECGs) were evaluated at protocol‐specified time points. Complete necropsy and histopathologic examinations were performed following humane euthanasia. Four buprenorphine‐treated cats experienced AEs during the study, two unrelated and two related to study drug administration. The two cats with AEs considered related to drug administration had clinical signs of hyperactivity, difficulty in handling, disorientation, agitation and dilated pupils in one 0.24 mg/kg/day cat and one 0.72 mg/kg/day cat. All of these clinical signs were observed simultaneously. There were no drug‐related effects on survival, injection response, injection site inspections, body weight, food or water consumption, bleeding time, urinalysis, respiration rate, heart rate, ECGs, blood pressures, body temperatures, macroscopic examinations or organ weights. Once daily buprenorphine s.c. injections at doses of 0.24, 0.72 and 1.20 mg/kg/day for 9 consecutive days were well tolerated in young domestic cats.     

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.     

Oral,subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy cats

Ondansetron is a 5‐HT₃ receptor antagonist that is an effective anti‐emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in healthy cats. Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross‐over manner with a 5‐day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 h after administration of ondansetron. Ondansetron concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Repeated measures anova was used to compare parameters between administration routes. Bioavailability of ondansetron was 32% (oral) and 75% (subcutaneous). Calculated elimination half‐life of ondansetron was 1.84 ± 0.58 h (intravenous), 1.18 ± 0.27 h (oral) and 3.17 ± 0.53 h (subcutaneous). The calculated elimination half‐life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. Subcutaneous administration of ondansetron to healthy cats is more bioavailable and results in a more prolonged exposure than oral administration. This information will aid management of emesis in feline patients.     

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 (40 μg/kg) and buprenorphine (20 μg/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 (C_max) were significantly lower following OTM than following i.m. administration. For buprenorphine, time to reach C_max was also significantly longer after OTM administration than after i.m. injection. Data suggested that dexmedetomidine (40 μg/kg) combined with buprenorphine (20 μg/kg) is not as well absorbed from the buccal mucosa site as from the intramuscular injection site.     

Limited sampling pharmacokinetics of subcutaneous ondansetron in healthy geriatric cats,cats with chronic kidney disease,and cats with liver disease

Ondansetron, a 5‐HT₃ receptor antagonist, is an effective anti‐emetic in cats. The purpose of this study was to compare pharmacokinetics of subcutaneous (SQ) ondansetron in healthy geriatric cats to cats with chronic kidney disease (CKD) or liver disease using a limited sampling strategy. 60 cats participated; 20 per group. Blood was drawn 30 and 120 min following one 2 mg ( mean 0.49 mg/kg , range 0.27–1.05 mg/kg ) SQ dose of ondansetron. Ondansetron concentrations were measured by liquid chromatography coupled to tandem mass spectrometry. Drug exposure represented as area under the curve (AUC) was predicted using a limited sampling approach based on multiple linear regression analysis from previous full sampling studies, and clearance (CL/F) estimated using noncompartmental methods. Kruskal–Wallis anova was used to compare parameters between groups. Mean AUC (ng/mL·h) of subcutaneous ondansetron was 301.4 (geriatric), 415.2 (CKD), and 587.0 (liver). CL/F (L/h/kg) of SQ ondansetron was 1.157 (geriatric), 0.967 (CKD), and 0.795 (liver). AUC was significantly higher in liver and CKD cats when compared to geriatric cats (P < 0.05). CL/F in liver cats was significantly decreased (P < 0.05) compared to geriatric cats. In age‐matched subset analysis, AUC and CL/F in liver cats remained significantly different from geriatric cats.     

Bioavailability of morphine,methadone, hydromorphone,and oxymorphone following buccal administration in cats

Buccal administration of buprenorphine is commonly used to treat pain in cats. It has been argued that absorption of buprenorphine through the buccal mucosa is high, in part due to its pKa of 8.24. Morphine, methadone, hydromorphone, and oxymorphone have a pKa between 8 and 9. This study characterized the bioavailability of these drugs following buccal administration to cats. Six healthy adult female spayed cats were used. Buccal pH was measured prior to drug administration. Morphine sulfate, 0.2 mg/kg IV or 0.5 mg/kg buccal; methadone hydrochloride, 0.3 mg/kg IV or 0.75 mg/kg buccal; hydromorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal; or oxymorphone hydrochloride, 0.1 mg/kg IV or 0.25 mg/kg buccal were administered. All cats received all treatments. Arterial blood was sampled immediately prior to drug administration and at various times up to 8 h thereafter. Bioavailability was calculated as the ratio of the area under the time–concentration curve following buccal administration to that following IV administration, each indexed to the administered dose. Mean ± SE (range) bioavailability was 36.6 ± 5.2 (12.7–49.5), 44.2 ± 7.9 (18.7–70.5), 22.4 ± 6.9 (6.4–43.4), and 18.8 ± 2.0 (12.9–23.5)% for buccal administration of morphine, methadone, hydromorphone, and oxymorphone, respectively. Bioavailability of methadone was significantly higher than that of oxymorphone.     

Comparative pharmacokinetics of intravenous fentanyl and buprenorphine in healthy greyhound dogs

The purpose of this study was to compare the pharmacokinetics of two highly protein‐bound, lipophilic opioid drugs. Fentanyl (10 μg/kg) and buprenorphine (20 μg/kg) were administered intravenously (IV) to six healthy greyhound dogs (three males and three females). The doses were based on clinically administered doses for dogs. Plasma drug concentrations were determined using liquid chromatography with mass spectrometry, and noncompartmental pharmacokinetics were estimated with computer software. The volume of distribution (area) was larger for fentanyl (7.42 L/kg) compared to buprenorphine (3.54 L/kg). The plasma clearance of fentanyl (38.6 mL·min/kg) was faster than buprenorphine (10.3 mL·min/kg). The terminal half‐life of fentanyl (2.22 h) was shorter than buprenorphine (3.96 h). Despite similar physicochemical properties including octanol–water partition coefficient and pKa, the pharmacokinetics of fentanyl and buprenorphine were not similar. Both fentanyl (84%) and buprenorphine (95–98%) are considered highly protein bound, but the differences in protein binding may contribute to the lack of similarity of pharmacokinetics in healthy dogs.     

Pharmacokinetics and distribution in interstitial and pulmonary epithelial lining fluid of danofloxacin in ruminant and preruminant calves

The objective of this study was to compare active drug concentrations in the plasma vs. different effector compartments including interstitial fluid (ISF) and pulmonary epithelial lining fluid (PELF) of healthy preruminating (3‐week‐old) and ruminating (6‐month‐old) calves. Eight calves in each age group were given a single subcutaneous (s.c.) dose (8 mg/kg) of danofloxacin. Plasma, ISF, and bronchoalveolar lavage (BAL) fluid were collected over 96 h and analyzed by high‐pressure liquid chromatography. PELF concentrations were calculated by a urea dilution assay of the BAL fluids. Plasma protein binding was measured using a microcentrifugation system. For most preruminant and ruminant calves, the concentration–time profile of the central compartment was best described by a two‐compartment open body model. For some calves, a third compartment was also observed. The time to maximum concentration in the plasma was longer in preruminating calves (3.1 h) vs. ruminating calves (1.4 h). Clearance (CL/F) was 385.15 and 535.11 mL/h/kg in preruminant and ruminant calves, respectively. Ruminant calves maintained higher ISF/plasma concentration ratios throughout the study period compared to that observed in preruminant calves. Potential reasons for age‐related differences in plasma concentration–time profiles and partitioning of the drug to lungs and ISF as a function of age are explored.     

Pharmacokinetics of fentanyl,alfentanil, and sufentanil in isoflurane‐anesthetized cats

The aim of this study was to compare the pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane‐anesthetized cats. Six adult cats were used. Anesthesia was induced and maintained with isoflurane in oxygen. End‐tidal isoflurane concentration was set at 2% and adjusted as required due to spontaneous movement. Fentanyl (10 μg/kg), alfentanil (100 μg/kg), or sufentanil (1 μg/kg) was administered intravenously as a bolus, on separate days. Blood samples were collected immediately before and for 8 h following drug administration. Plasma drug concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to concentration–time data. A 3‐compartment model best fitted the concentration–time data for all drugs, except for 1 cat in the sufentanil group (excluded from analysis). The volume of the central compartment and the volume of distribution at steady‐state (L/kg) [mean ± SEM (range)], the clearance (mL/min/kg) [harmonic mean ± pseudo‐SD (range)], and the terminal half‐life (min) [median (range)] were 0.25 ± 0.04 (0.09–0.34), 2.18 ± 0.16 (1.79–2.83), 18.6 ± 5.0 (15–29.8), and 151 (115–211) for fentanyl; 0.10 ± 0.01 (0.07–0.14), 0.89 ± 0.16 (0.68–1.83), 11.6 ± 2.6 (9.2–15.8), and 144 (118–501) for alfentanil; and 0.06 ± 0.01 (0.04–0.10), 0.77 ± 0.07 (0.63–0.99), 17.6 ± 4.3 (13.9–24.3), and 54 (46–76) for sufentanil. Differences in clearance and volume of distribution result in similar terminal half‐lives for fentanyl and alfentanil, longer than for sufentanil.     

Chrysomya bezziana (Diptera: Calliphoridae) infestation in two Malaysian cats treated with oral lotilaner

The most common fly species associated with screwworm myiasis in Southeast Asia is Chrysomya bezziana (Ch. bezziana), the Old‐World screwworm. Treatment of screwworm myiasis in cats traditionally has comprised subcutaneous injection of ivermectin or oral administration of nitenpyram, combined with aggressive tissue debridement and larval removal under general anaesthesia. Two cats diagnosed with cutaneous myiasis caused by the larvae of Ch. bezziana were treated with lotilaner. In both cats, a single dose of lotilaner at 6–26 mg/kg, killed all larvae within 24 h, negating the need for general anaesthesia. Both cats were simultaneously infested with Lynxacarus radovskyi (L. radovskyi) which also was eradicated with lotilaner. No adverse reactions were observed and both cats recovered without complications.     

Ronidazole pharmacokinetics in cats following delivery of a delayed‐release guar gum formulation

Ronidazole (RDZ) is the only known effective treatment for feline diarrhea caused by Tritrichomonas foetus. This study aimed to develop guar gum‐coated colon‐targeted tablets of RDZ and to determine the pharmacokinetics of this delayed‐release formulation in cats. Guar gum‐coated tablets were administered orally once to five healthy cats (mean dose 32.3 mg/kg). The tablets were then administered once daily for 5 days to four cats (mean dose 34.5 mg/kg), and absorption studies repeated on day 5. Plasma was collected and analyzed for RDZ concentration, and pharmacokinetic noncompartmental and deconvolution analysis were performed on the data. There was negligible RDZ release until after 6 h, and a delayed peak plasma concentration (mean C_max 28.9 μg/mL) at approximately 14.5 h, which coincides with colonic arrival in cats. Maximum input rate (mg/kg per hour) occurred between 6 and 16 h. This delayed release of ronidazole from guar gum‐coated tablets indicates that release of RDZ may be delayed to deliver the medication to a targeted area of the intestine. Repeated dosing with guar gum tablets to steady‐state did not inhibit drug bioavailability or alter the pharmacokinetics. Such targeted RDZ drug delivery may provide improved efficacy and reduce adverse effects in cats.     

Differential pharmacokinetics and pharmacokinetic/pharmacodynamic modelling of robenacoxib and ketoprofen in a feline model of inflammation

Robenacoxib and ketoprofen are acidic nonsteroidal anti‐inflammatory drugs (NSAIDs). Both are licensed for once daily administration in the cat, despite having short blood half‐lives. This study reports the pharmacokinetic/pharmacodynamic (PK/PD) modelling of each drug in a feline model of inflammation. Eight cats were enrolled in a randomized, controlled, three‐period cross‐over study. In each period, sterile inflammation was induced by the injection of carrageenan into a subcutaneously implanted tissue cage, immediately before the subcutaneous injection of robenacoxib (2 mg/kg), ketoprofen (2 mg/kg) or placebo. Blood samples were taken for the determination of drug and serum thromboxane (Tx)B₂ concentrations (measuring COX‐1 activity). Tissue cage exudate samples were obtained for drug and prostaglandin (PG)E₂ concentrations (measuring COX‐2 activity). Individual animal pharmacokinetic and pharmacodynamic parameters for COX‐1 and COX‐2 inhibition were generated by PK/PD modelling. S(+) ketoprofen clearance scaled by bioavailability (CL/F) was 0.114 L/kg/h (elimination half‐life = 1.62 h). For robenacoxib, blood CL/F was 0.684 L/kg/h (elimination half‐life = 1.13 h). Exudate elimination half‐lives were 25.9 and 41.5 h for S(+) ketoprofen and robenacoxib, respectively. Both drugs reduced exudate PGE₂ concentration significantly between 6 and 36 h. Ketoprofen significantly suppressed (>97%) serum TxB₂ between 4 min and 24 h, whereas suppression was mild and transient with robenacoxib. In vivoIC₅₀COX‐1/IC₅₀COX‐2 ratios were 66.9:1 for robenacoxib and 1:107 for S(+) ketoprofen. The carboxylic acid nature of both drugs may contribute to the prolonged COX‐2 inhibition in exudate, despite short half‐lives in blood.     

Clinical effect of buprenorphine or butorphanol,in combination with detomidine and diazepam,on sedation and postoperative pain after cheek tooth extraction in horses

The objective of this study was to compare effects of butorphanol (BUT) or buprenorphine (BUP), in combination with detomidine and diazepam, on the sedation quality, surgical conditions, and postoperative pain control after cheek tooth extraction in horses, randomly allocated to 2 treatment groups (BUT: n = 20; BUP: n = 20). A bolus of detomidine (15 μg/kg, IV) was followed by either BUP (7.5 μg/kg, IV) or BUT (0.05 mg/kg, IV). After 20 min, diazepam (0.01 mg/kg, IV) was administered and sedation was maintained with a detomidine IV infusion (20 μg/kg/h), with rate adjusted based on scores to 5 variables. All horses received a nerve block (maxillary or mandibular), and gingival infiltration with mepivacaine. Sedation quality was assessed by the surgeon from 1 (excellent) to 10 (surgery not feasible). A pain scoring system (EQUUS-FAP) was used to assess postoperative pain. Serum cortisol concentrations and locomotor activity (pedometers) were measured.Horses in BUP and BUT required a median detomidine infusion rate of 30.2 μg/kg/h (20 to 74.4 μg/kg/h) and 32.2 μg/kg/h (20 to 48.1 μg/kg/h), respectively (P = 0.22). Horses in the BUP group had better sedation quality (P < 0.05) during surgery and higher step counts (P < 0.001) postoperatively. Buprenorphine combined with detomidine provided a more reliable sedation than butorphanol. However, the EQUUS-FAP pain scale became unreliable because of BUP-induced excitement behavior.     

Comparison of the pharmacokinetics and thermal antinociceptive pharmacodynamics of 20 µg kg−1 buprenorphine administered sublingually or intravenously in cats

Little is known about the analgesic action of buprenorphine (BUP) in cats. Relative to man, the cat has a more alkaline oral pH, which may make this an effective route for administering BUP in this species. This study aimed to assess and compare the pharmacokinetics and pharmacodynamics of sublingual (S‐L) and IV administration of BUP. Thermal threshold (TT) was measured and blood samples were collected following IV or S‐L administration (20 µg kg^?1) of the injectable formulation. Six cats (five spayed females, one castrated male, 4.1–6.6 kg) were used. Each cat received both treatments in a randomized cross‐over study design with 1 month between experiments. Twenty‐four hours prior to each study, the lateral thorax of each of the cats was shaved, cephalic and jugular catheters placed, and oral pH measured. On the day of the study, TT was measured using a ‘thorax‐mounted’ thermal threshold‐testing device specifically developed for cats. The cats were free to move around. Skin temperature was recorded before each test, then the heater activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. The thermal threshold cut‐off point was 55.5 °C. Three baseline thresholds were recorded before treatment with S‐L or IV (via cephalic catheter) BUP (20 µg kg^?1). Blood was withdrawn (jugular) at 1, 2, 4, 6, 10, 15, 30, 45, 60 minutes and at 2, 4, 6, 8, 12, and 24 hours post‐administration. TT was measured every 30 minutes?6 hours, 1–12 hours, and at 24 hours post‐administration. Plasma was immediately separated, stored at ?20.5 °C, and assayed within 4 months using a commercially available ¹²⁵I radioimmunoassay. Threshold data were analyzed using anova with a repeat factor of time. No adverse effects were noted. Pupils were dilated for up to 9 hours post‐BUP. Behavioral changes were calm euphoria. Measured oral pH was 9 in each cat. Pre‐treatment mean threshold (±SD) was 41.2 ± 0.9 °C in the S‐L group and 40.8 ± 0.85 °C in the IV group. There were no significant differences between the groups with respect to thresholds over time (p = 0.72). Thresholds were significantly increased from 30 to 360 minutes in both the groups (>44.615 °C). Peak plasma BUP (C_max) was lower (11 ± 6.7 ng mL^?1vs. 92.9 ± 107.9 ng mL^?1) and occurred later (T_max) (30 minutes vs. 1 minute) after S‐L compared to IV administration, respectively. BUP (20 µg kg^?1)‐administered S‐L or IV provided antinociception between 30 and 360 minutes after administration. Plasma levels did not correspond to TT.     

Comparative Pharmacokinetics of Enrofloxacin and Tissue Concentrations of Parent Drug and Ciprofloxacin after Intramuscular Administrations of Free and Liposome‐Encapsulated Enrofloxacin in Rabbits

Pharmacokinetic properties and tissue concentrations of enrofloxacin and ciprofloxacin were compared after intramuscular (i.m.) administrations of free and liposome‐encapsulated enrofloxacin at the dose of 5 mg/kg body weight (bw). Twelve healthy adult New Zealand white rabbits were used in the experiment. Blood samples were obtained at 10, 20, 40, 60 and 90 min and 2, 4, 6, 8 and 12 h and tissue samples were collected 24 h after injection. Concentrations of drugs in serum were determined by high‐performance liquid chromatography. Pharmacokinetics were best described by a two‐compartment open model. Results indicated that absorption rate was slow, peak concentration was higher (P < 0.05), and the time to peak concentration (t_max ? 1.5 h) was significantly longer (P < 0.05) for liposome‐encapsulated enrofloxacin (LEE) when compared with free enrofloxacin. Values of elimination half‐life (t_1/2β = 12.9 h) and mean residence time (MRT = 17.6 h) of liposome‐encapsulated enrofloxacin were longer (P < 0.05) and total clearance (Cl = 0.43 l/h/kg) was lower than those of free form. Moreover, the distribution volume at steady‐state (V_d(ss) = 14.4 l/kg) of enrofloxacin administered encapsulated into liposomes was significantly higher (P < 0.05) than that of free enrofloxacin (FE). The tissue levels of enrofloxacin and ciprofloxacin after LEE injection were not different (P > 0.05) from FE. In conclusion, the result of present study suggest that LEE may be a beneficial and valuable formulation in the treatment of infectious diseases caused by sensitive pathogens in animals, providing sustained drug release from injection side and prolonged therapeutic serum concentrations after i.m. administration.     

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.     

Serum concentrations of buprenorphine after oral and parenteral administration in male mice

Buprenorphine is the most commonly used drug for peri-operative pain relief in laboratory rodents. The systemic concentrations of buprenorphine were measured in mice following administration intravenously (IV), subcutaneously (SC), orally by gavage and by voluntary ingestion, to determine the post-administration serum concentration of buprenorphine. Voluntarily ingested buprenorphine resulted in long-lasting high serum concentrations, as did oral gavage administration (24 h serum concentration: 110 ng h/mL for both routes of administration). In contrast, buprenorphine administered parenterally remained in the circulation for a substantially shorter time (24 h serum concentration for IV and SC were 40 ng h/mL and 30 ng h/mL, respectively). This marked difference was probably due to the higher dose used for oral administration, which is regarded necessary for sufficient analgesic effect, and to the slower absorption of the oral boli, as well as saturation of the hepatic buprenorphine metabolising pathways. Voluntary ingestion of buprenorphine was found to constitute a practical way to provide laboratory mice with efficient pain relief.     

Associations between meal size,gastric emptying and post‐prandial plasma glucose,insulin and lactate concentrations in meal‐fed cats

Plasma glucose and insulin concentrations are increased for 12–24 h in healthy cats following moderate‐ to high‐carbohydrate meals. This study investigated associations between gastric emptying time and post‐prandial plasma glucose, insulin and lactate concentrations in cats fed an extruded dry, high‐carbohydrate, moderate‐fat, low‐protein diet (51, 28, 21% metabolizable energy, respectively) once daily by varying meal volume. Eleven healthy, non‐obese, neutered adult cats were enrolled in a prospective study and fed to maintain body weight. Ultrasound examinations were performed for up to 26 h, and blood collections over 24 h after eating meals containing approximately 100% and 50% of the cats’ daily caloric intake (209 and 105 kJ/kg BW, respectively). Gastric emptying time was increased after a meal of 209 kJ/kg BW compared with 105 kJ/kg BW (median gastric emptying times 24 and 14 h, respectively; p = 0.03). Time for glucose to return to fasting was longer after the 209 kJ/kg BW meal (median 20 h; 25th and 75th percentiles 15 and 23 h, respectively) than the 105 kJ/kg BW meal (13, 12 and 14 h; p < 0.01); however, peak glucose was not higher after the 209 kJ/kg BW meal compared with the 105 kJ/kg BW meal [(mean ± SD) 6.6 ± 0.6 and 7.8 ± 1.2 mmol/l, respectively, p = 0.07]. Times for insulin to return to fasting were not significantly longer after the 209 kJ/kg BW meal than the 105 kJ/kg BW meal (p = 0.29). d ‐ and l ‐lactate concentrations were not associated with gastric emptying time or post‐prandial blood glucose and insulin. Based on results obtained, prolonged gastric emptying contributes to prolonged post‐prandial hyperglycemia in cats meal fed a high‐carbohydrate, low‐protein, dry diet and fasting times for cats’ meal‐fed diets of similar composition should be 14–26 h, depending on meal size.