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OBJECTIVE To determine the pharmacokinetics of detomidine hydrochloride administered IV (as an injectable formulation) or by the oral-transmucosal (OTM) route (as a gel) and assess sedative effects of the OTM treatment in healthy dogs.
ANIMALS 12 healthy adult dogs.
PROCEDURES In phase 1, detomidine was administered by IV (0.5 mg/m2) or OTM (1 mg/m2) routes to 6 dogs. After a 24-hour washout period, each dog received the alternate treatment. Blood samples were collected for quantification via liquid chromatography with mass spectrometry and pharmacokinetic analysis. In phase 2, 6 dogs received dexmedetomidine IV (0.125 mg/m2) or detomidine gel by OTM administration (0.5 mg/m2), and sedation was measured by a blinded observer using 2 standardized sedation scales while dogs underwent jugular catheter placement. After a l-week washout period, each dog received the alternate treatment.
RESULTS Median maximum concentration, time to maximum concentration, and bioavailability for detomidine gel following OTM administration were 7.03 ng/mL, 1.00 hour, and 34.52%, respectively; harmonic mean elimination half-life was 0.63 hours. All dogs were sedated and became laterally recumbent with phase 1 treatments. In phase 2, median global sedation score following OTM administration of detomidine gel was significantly lower (indicating a lesser degree of sedation) than that following IV dexmedetomidine treatment; however, total sedation score during jugular vein catheterization did not differ between treatments. The gel was subjectively easy to administer, and systemic absorption was sufficient for sedation.
CONCLUSIONS AND CLINICAL RELEVANCE Detomidine gel administered by the OTM route provided sedation suitable for a short, minimally invasive procedure in healthy dogs.
OBJECTIVE To evaluate hemodynamic, respiratory, and sedative effects of buccally administered detomidine gel and reversal with atipamezole in dogs.
ANIMALS 8 adult purpose-bred dogs.
PROCEDURES Arterial and venous catheters were placed. Baseline heart rate, respiratory rate, cardiac output (determined via lithium dilution with pulse contour analysis), oxygen delivery, systemic vascular resistance, arterial blood gas values, and sedation score were obtained. Detomidine gel (2.0 mg/m2) was administered on the buccal mucosa. Cardiopulmonary data and sedation scores were obtained at predetermined times over 180 minutes. Atipamezole (0.1 mg/kg) was administered IM at 150 minutes. Reversal of sedation was timed and scored. Data were analyzed with an ANOVA.
RESULTS Compared with baseline values, heart rate was lower at 45 to 150 minutes, cardiac output and oxygen delivery were lower at 30 to 150 minutes, and systemic vascular resistance was increased at 30 to 150 minutes. There were no significant changes in Paco 2, Pao 2, or lactate concentration at any time point, compared with baseline values, except for lactate concentration at 180 minutes. All dogs became sedated; maximum sedation was detected 75 minutes after administration of detomidine. Mean ± SD time to recovery after atipamezole administration was 7.55 ± 1.89 minutes; sedation was completely reversed in all dogs. No adverse events were detected.
CONCLUSIONS AND CLINICAL RELEVANCE Buccally administered detomidine gel was associated with reliable and reversible sedation in dogs, with hemodynamic effects similar to those induced by other α2-adrenoceptor agonists. Buccally administered detomidine gel could be an alternative to injectable sedatives in healthy dogs.
Case Description—A 1-year-old spayed female mixed-breed dog was evaluated because of urinary incontinence, polyuria, polydipsia, and minimally concentrated urine.
Clinical Findings—Markedly high circulating alanine transaminase activity, mildly high circulating alkaline phosphatase activity, and low urine specific gravity were detected for the dog. Results of ultrasonographic examination of the abdomen and cytologic examination of liver samples were unremarkable. Carprofen was detected in serum and plasma samples obtained from the dog. Exposure to carprofen was attributed to ingestion of feces of another dog in the household that was receiving the drug daily.
Treatment and Outcome—Access to feces of other dogs in the household was prevented; no other treatment was initiated. Urinary incontinence, polyuria, and polydipsia resolved, and urine specific gravity increased within 7 days following discontinuation of consumption of feces. Alanine transaminase activity was substantially lower than the value determined during the initial examination, and alkaline phosphatase activity was within the reference range 5 weeks after discontinuation of consumption of feces by the dog.
Clinical Relevance—Findings for the dog of this report suggested that carprofen toxicosis can be caused by consumption of feces of another dog receiving the drug. This cause of adverse effects should be a differential diagnosis for dogs with clinical signs and clinicopathologic abnormalities consistent with carprofen toxicosis.
To compare the analgesic efficacy of grapiprant to carprofen for the treatment of postoperative pain and inflammation in dogs following ovariohysterectomy.
12 purpose-bred adult sexually intact female Beagles.
Dogs were randomly assigned to 1 of 2 treatment groups: grapiprant (2 mg/kg, PO; n = 6) or carprofen (4.4 mg/kg, PO; n = 6), 1.5 hours prior to ovariohysterectomy (OVH) and every 24 hours afterward for 3 total doses. An ultrafiltration probe was placed within the OVH incision to collect interstitial fluid (ISF). Pain and inflammation were assessed by masked investigators via mechanical nociceptive threshold testing and the short form of the Glasgow Composite Pain Scale before drug administration and at multiple time points for 72 hours following dosing and surgery. ISF samples were collected at the same time points to assess prostaglandin E2 concentrations at the site of inflammation.
In both groups, pain scale scores were highest in the immediate postoperative period and decreased over time. In both treatment groups, there were significant (P = 0.003) differences in mechanical nociceptive threshold results over time when compared with baseline, but there was no difference between groups. Prostaglandin E2 concentrations in ISF were higher in dogs receiving grapiprant compared with carprofen (P < 0.001). One dog in the carprofen group required rescue analgesia.
Results of this preliminary study suggested both carprofen and grapiprant may be effective for postoperative pain following OVH in dogs; however, additional studies are warranted to determine grapiprant’s effectiveness in a larger and more diverse population of dogs.
To evaluate the effect of a constant rate infusion of ketamine on cardiac index (CI) in sheep, as estimated using noninvasive cardiac output (NICO) monitoring by partial carbon dioxide rebreathing, when anesthetized with sevoflurane at the previously determined minimum alveolar concentration that blunts adrenergic responses (MACBAR).
12 healthy Dorset-crossbred adult sheep.
Sheep were anesthetized 2 times in a balanced placebo-controlled crossover design. Anesthesia was induced with sevoflurane delivered via a tight-fitting face mask and maintained at MACBAR. Following induction, sheep received either ketamine (1.5 mg/kg IV, followed by a constant rate infusion of 1.5 mg/kg/h) or an equivalent volume of saline (0.9% NaCl) solution (placebo). After an 8-day washout period, each sheep received the alternate treatment. NICO measurements were performed in triplicate 20 minutes after treatment administration and were converted to CI. Blood samples were collected prior to the start of NICO measurements for analysis of ketamine plasma concentrations. The paired t test was used to compare CI values between groups and the ketamine plasma concentrations with those achieved during the previous study.
Mean ± SD CI of the ketamine and placebo treatments were 2.69 ± 0.65 and 2.57 ± 0.53 L/min/m2, respectively. No significant difference was found between the 2 treatments. Mean ketamine plasma concentration achieved prior to the NICO measurement was 1.37 ± 0.58 µg/mL, with no significant difference observed between the current and prior study.
Ketamine, at the dose administered, did not significantly increase the CI in sheep when determined by partial carbon dioxide rebreathing.
OBJECTIVE To evaluate quality of recovery from general anesthesia in horses after induction with propofol and ketamine versus midazolam and ketamine.
DESIGN Prospective randomized crossover study.
ANIMALS 6 healthy adult horses.
PROCEDURES Horses were premedicated with xylazine (1.0 mg/kg [0.45 mg/lb], IV), and general anesthesia was induced with midazolam (0.1 mg/kg [0.045 mg/lb], IV) or propofol (0.5 mg/kg [0.23 mg/lb], IV), followed by ketamine (3.0 mg/kg [1.36 mg/lb], IV). Horses were endotracheally intubated, and anesthesia was maintained with isoflurane. After 60 minutes, horses were given romifidine (0.02 mg/kg [0.009 mg/lb], IV) and allowed to recover unassisted. Times to first movement, sternal recumbency, and standing and the number of attempts to stand were recorded. Plasma concentrations of propofol or midazolam were measured following induction and immediately before recovery. Recovery quality was scored by 3 graders with a recovery rubric and a visual analog scale.
RESULTS Number of attempts to stand was significantly lower when horses received propofol (median, 2; range, 1 to 3) than when they received midazolam (median, 7.5; range, 3 to 16). For both the recovery rubric and visual analog scale, recovery quality was significantly better when horses received propofol than when they received midazolam. Plasma drug concentration at recovery, as a percentage of the concentration at induction, was significantly lower when horses received propofol than when they received midazolam.
CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that for horses undergoing short (ie, 60 minutes) periods of general anesthesia, recovery quality may be better following induction with propofol and ketamine, compared with midazolam and ketamine.
OBJECTIVE To investigate in vitro carboplatin release from 6 carrier media.
SAMPLE 6 carboplatin-containing carrier media.
PROCEDURES An in vitro release study was performed with 6 commercially available carrier media: a hemostatic gelatin sponge, a poloxamer copolymer gel, and 2 sizes (3 and 4.8 mm in diameter) of beads molded from each of 2 commercial calcium sulfate products. All carrier media contained 10 mg of carboplatin. Carrier media specimens were placed in 37°C PBS solution for 96 hours. Carboplatin concentrations in PBS solution were measured by use of high-performance liquid chromatography at 15 time points to calculate the amount and proportion of carboplatin released from each specimen.
RESULTS Peak release of carboplatin from the poloxamer copolymer gel and hemostatic gelatin sponge were achieved after 4 and 20 hours, respectively. Maximum release did not differ significantly between the poloxamer copolymer gel and hemostatic gelatin sponge, but both released significantly more carboplatin within 96 hours than did both of the commercial calcium sulfate products. The poloxamer copolymer gel released 99% of the carboplatin, and the hemostatic gelatin sponge released 68.5% of the carboplatin. Peak release of carboplatin from the calcium sulfate beads was not reached within 96 hours.
CONCLUSIONS AND CLINICAL RELEVANCE In this study, carboplatin release from the hemostatic gelatin sponge was incomplete. The poloxamer copolymer gel and hemostatic gelatin sponge released carboplatin rapidly in vitro, whereas calcium sulfate beads did not.
To investigate the feasibility and pharmacokinetics of cytarabine delivery as a subcutaneous continuous-rate infusion with the Omnipod system.
6 client-owned dogs diagnosed with meningoencephalomyelitis of unknown etiology were enrolled through the North Carolina State University Veterinary Hospital.
Cytarabine was delivered at a rate of 50 mg/m2/hour as an SC continuous-rate infusion over 8 hours using the Omnipod system. Plasma samples were collected at 0, 4, 6, 8, 10, 12, and 14 hours after initiation of the infusion. Plasma cytarabine concentrations were measured by high-pressure liquid chromatography. A nonlinear mixed-effects approach generated population pharmacokinetic parameter estimates.
The mean peak plasma concentration (Cmax) was 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL), average time to Cmax was 7 hours (range, 4 to 8 hours; SD, 1.67 hours), terminal half-life was 1.13 hours (SD, 0.29 hour), and the mean area under the curve was 52,996.82 hours X μg/mL (range, 35,963.67 to 71,848.37 hours X μg/mL; SD, 12,960.90 hours X μg/mL). Cmax concentrations for all dogs were more than 1,000 ng/mL (1.0 μg/mL) at the 4-, 6-, 8-, and 10-hour time points.
An SC continuous-rate infusion of cytarabine via the Omnipod system is feasible in dogs and was able to achieve a steady-state concentration of more than 1 μg/mL 4 to 10 hours postinitiation of cytarabine and a Cmax of 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL). These are comparable to values reported previously with IV continuous-rate infusion administration in healthy research Beagles and dogs with meningoencephalomyelitis of unknown etiology.