Pharmacokinetic Profiles of a New Extended-release Buprenorphine Formulation in Cynomolgus Macaques (Macaca fascicularis).

The primary objective of this study was to evaluate the pharmacokinetic profile of a new extended-release formulation of buprenorphine (BupBaseER) at a dose that would produce pain management of the desired duration. A secondary objective was to compare the incidence of injection site reactions between the original extended-release formulation (BupHClER) and BupBaseER, which uses a different proprietary polymer-based vehicle than does the BupHClER formulation. Eighteen cynomolgus macaques (M. fascicularis) were divided into 2 groups. Each macaque in the first group (n = 6) received a single subcutaneous injection of 0.06 mg/kg BupBaseER (10 mg/mL) followed at least 2 wk later by a single subcutaneous injection of 0.12 mg/kg. Animals in group 2 (n = 12) received 2 injections of each of 3 compounds-the original polymer matrix vehicle used in BupHClER, the modified polymer matrix vehicle used in BupBaseER, and 0.9% saline-in designated areas of the dorsoscapular region. The 0.06- and 0.12-mg/kg doses both maintained therapeutic levels that were 3 times higher than the hypothesized analgesic threshold of 0.1 ng/mL. These doses maintained therapeutic level for approximately 44 and 103 h, respectively. Based on these data, buprenorphine concentration likely remains well above the therapeutic threshold beyond the 120 h span of this study. During the 30 d after administration, one macaque had a mild skin reaction to BupHClER. None of the animals in either group had skin reactions to BupBaseER at either dosage. These findings support the use of BupBaseER to provide pain management, promote animal welfare, decrease animal stress, and simplify the postoperative management of NHP in research and zoological settings.

Structure-activity relationships and hepatic safety risks of thiazole agonists of the thrombopoietin receptor.

5-F substitution of an aminothiazole moiety within a series of thrombopoietin receptor agonists leads to potent agents with an improved hepatic safety profile in rodent toxicology studies.

A comparison of xylazine and medetomidine in an anesthetic combination in New Zealand White Rabbits.

A comparison was made of two anesthetic protocols for cardiothoracic surgery in rabbits. Eight male New Zealand White rabbits (2.8 to 3.2 kg) were used in a double crossover study. Each rabbit received intramuscular ketamine (35 mg/kg), xylazine (5 mg/kg), and buprenorphine (0.03 mg/kg) or ketamine (35 mg/kg), medetomidine (0.5 mg/kg), and buprenorphine (0.03 mg/kg) on alternate weeks. After intramuscular injection, each rabbit was intubated and placed on 0.75% isoflurane in 1 L O2/min. Palpebral, pedal, and righting reflexes and cardiopulmonary parameters were measured every minute for the first 10 min and every 5 min thereafter. Rabbits were monitored for 20 min of spontaneous ventilation followed by 60 min of intermittent positive pressure ventilation. Intermittent positive pressure ventilation and isoflurane then were discontinued and recovery monitored. Systolic, mean, and diastolic blood pressures were higher in the medetomidine-treated rabbits. Return of the palpebral, pedal, and righting reflexes was prolonged in the medetomidine-treated rabbits. There were no differences in heart rate, respiratory rate, return to spontaneous breathing, and time to extubation between the two groups. These results indicate medetomidine can be safely used in rabbit anesthesia, provides acceptable cardiovascular parameters, and induces a longer anesthetic period than that of xylazine.