Therapeutic efficacy and pharmacokinetics of liposomal-cannabidiol injection: a pilot clinical study in dogs with naturally-occurring osteoarthritis

IntroductionOsteoarthritis is a common disease in dogs resulting in chronic pain and decreased wellbeing. Common analgesics such as non-steroidal anti-inflammatories may fail to control pain and can produce major adverse effects. Study objectives were to evaluate pharmacokinetics, therapeutic efficacy, and safety of subcutaneous liposomal-cannabidiol (CBD) as an additional analgesic therapy in dogs suffering from naturally-occurring osteoarthritis.MethodsSix such dogs were recruited following ethics approval and owner consent. Dogs were administered a single subcutaneous injection of 5 mg/kg liposomal-CBD. Plasma concentrations of CBD, blood work, activity monitoring collar data, wellbeing questionnaire (owners) and pain scoring (veterinarian) were performed at baseline and monitored up to six weeks following intervention. Data overtime were compared with baseline using linear-regression mixed-effects. P-value was set at 0.05.ResultsCBD plasma concentrations were observed for 6 weeks; median (range) peak plasma concentration (Cmax) was 45.2 (17.8–72.5) ng/mL, time to Cmax was 4 (2–14) days and half-life was 12.4 (7.7–42.6) days. Median (range) collar activity score was significantly increased on weeks 5–6; from 29 (17–34) to 34 (21–38). Scores of wellbeing and pain evaluations were significantly improved at 2–3 weeks; from 69 (52–78) to 53.5 (41–68), and from 7.5 (6–8) to 5.5 (5–7), respectively. The main adverse effect was minor local swelling for several days in 5/6 dogs.ConclusionLiposomal-CBD administered subcutaneously produced detectable CBD plasma concentrations for 6 weeks with minimal side effects and demonstrated reduced pain and increased wellbeing as part of multimodal pain management in dogs suffering from osteoarthritis. Further placebo-controlled studies are of interest

Pharmacokinetics of butorphanol in male neutered cats anesthetized with isoflurane.

This study characterized the pharmacokinetics of butorphanol in cats anesthetized with isoflurane. Six young healthy male neutered cats were used. Cats were anesthetized with isoflurane in oxygen. Catheters were placed in a jugular vein for blood sampling and in a medial saphenous vein for butorphanol and lactated Ringer's solution administration. Butorphanol tartrate (1 mg/kg over 5 min) was administered intravenously. Blood samples were collected prior to butorphanol administration and at various times up to 365 min following administration. Plasma butorphanol concentration was measured using liquid chromatography/tandem mass spectrometry. Compartment models were fitted to the time-concentration data using nonlinear mixed effect modeling. A three-compartment model best fitted the data. Typical value (% interindividual variability) for the three volumes of distribution, the metabolic clearance, and the two distribution clearances were 230 (72), 1095 (not estimated), and 2596 (not estimated) ml/kg, and 18.4 (72), 169.6 (52), and 55.0 (43), respectively. Pharmacokinetic simulation suggested that a loading dose (µg/kg) calculated as 0.287 × target plasma concentration in ng/ml (CT ) followed by intravenous infusions (µg/kg/min) of 0.098 × CT for 20 min, 0.049 × CT for 40 min, and 0.022 × CT thereafter would rapidly achieve and maintain CT  ± 10% for up to 6.5 h

Plasma bupivacaine concentrations following orbital injections in cats.

ObjectiveTo determine plasma bupivacaine concentrations after retrobulbar or peribulbar injection of bupivacaine in cats.Study designRandomized, crossover, experimental trial with a 2 week washout period.AnimalsSix adult healthy cats, aged 1-2 years, weighing 4.6 ± 0.7 kg.MethodsCats were sedated by intramuscular injection of dexmedetomidine (36-56 μg kg-1) and were administered a retrobulbar injection of bupivacaine (0.75 mL, 0.5%; 3.75 mg) and iopamidol (0.25 mL), or a peribulbar injection of bupivacaine (1.5 mL, 0.5%; 7.5 mg), iopamidol (0.5 mL) and 0.9% saline (1 mL) via a dorsomedial approach. Blood (2 mL) was collected before and at 5, 10, 15, 22, 30, 45, 60, 120, 240 and 480 minutes after bupivacaine injection. Atipamezole was administered approximately 30 minutes after bupivacaine injection. Plasma bupivacaine and 3-hydroxybupivacaine concentrations were determined using liquid chromatography-mass spectrometry. Bupivacaine maximum plasma concentration (Cmax) and time to Cmax (Tmax) were determined from the data.ResultsThe bupivacaine median (range) Cmax and Tmax were 1.4 (0.9-2.5) μg mL-1 and 17 (4-60) minutes, and 1.7 (1.0-2.4) μg mL-1, and 28 (8-49) minutes, for retrobulbar and peribulbar injections, respectively. In both treatments the 3-hydroxybupivacaine peak concentration was 0.05-0.21 μg mL-1.Conclusions and clinical relevanceIn healthy cats, at doses up to 2 mg kg-1, bupivacaine peak plasma concentrations were approximately half that reported to cause arrhythmias or convulsive electroencephalogram (EEG) activity in cats, and about one-sixth of that required to produce hypotension

Plasma bupivacaine concentrations following orbital injections in cats

ObjectiveTo determine plasma bupivacaine concentrations after retrobulbar or peribulbar injection of bupivacaine in cats.Study designRandomized, crossover, experimental trial with a 2 week washout period.AnimalsSix adult healthy cats, aged 1-2 years, weighing 4.6 ± 0.7 kg.MethodsCats were sedated by intramuscular injection of dexmedetomidine (36-56 μg kg-1) and were administered a retrobulbar injection of bupivacaine (0.75 mL, 0.5%; 3.75 mg) and iopamidol (0.25 mL), or a peribulbar injection of bupivacaine (1.5 mL, 0.5%; 7.5 mg), iopamidol (0.5 mL) and 0.9% saline (1 mL) via a dorsomedial approach. Blood (2 mL) was collected before and at 5, 10, 15, 22, 30, 45, 60, 120, 240 and 480 minutes after bupivacaine injection. Atipamezole was administered approximately 30 minutes after bupivacaine injection. Plasma bupivacaine and 3-hydroxybupivacaine concentrations were determined using liquid chromatography-mass spectrometry. Bupivacaine maximum plasma concentration (Cmax) and time to Cmax (Tmax) were determined from the data.ResultsThe bupivacaine median (range) Cmax and Tmax were 1.4 (0.9-2.5) μg mL-1 and 17 (4-60) minutes, and 1.7 (1.0-2.4) μg mL-1, and 28 (8-49) minutes, for retrobulbar and peribulbar injections, respectively. In both treatments the 3-hydroxybupivacaine peak concentration was 0.05-0.21 μg mL-1.Conclusions and clinical relevanceIn healthy cats, at doses up to 2 mg kg-1, bupivacaine peak plasma concentrations were approximately half that reported to cause arrhythmias or convulsive electroencephalogram (EEG) activity in cats, and about one-sixth of that required to produce hypotension