Anesthetic and analgesics are essential components of both clinical and research procedures completed in marmosets. A review of current anesthetic and analgesic regimens for marmosets has been complied to provide a concise reference for veterinarians and investigator teams. Published dose regimens for injectable and inhalant anesthetic drugs and analgesic drugs are included. Appropriate physiological monitoring is key to the success of the procedure and perianesthetic options are provided. Although recent publications have refined anesthesia and analgesia practices, our review demonstrates the continued need for evidence-based resources specific to marmosets.

Current Topics in Marmoset Anesthesia and Analgesia.

Buprenorphine is an essential component of analgesic protocols in common marmosets (Callithrix jacchus). The use of buprenorphine HCl (BUP) and sustained-release buprenorphine (BSR) formulations has become commonplace in this species, but the pharmacokinetics have not been evaluated. Healthy adult (age, 2.4 to 6.8 y; 6 female and 6 male) common marmosets were enrolled in this study to determine the pharmacokinetic parameters, plasma concentration-time curves, and any apparent adverse effects of these compounds. Equal numbers of each sex were randomly assigned to receive BUP (0.02 mg/kg IM) or BSR (0.2 mg/kg SC), resulting in peak plasma concentrations (mean ± 1 SD) of 15.2 ± 8.1 and 2.8 ± 1.2 ng/mL, terminal phase t1/2 of 2.2 ± 1.0 and 32.6 ± 9.6 h, and AUC0-last of 16.1 ± 3.7 and 98.6 ± 42.7 ng × h/mL. The plasma concentrations of buprenorphine exceeded the proposed minimal therapeutic threshold (0.1 ng/mL) at 5 and 15 min after BUP and BSR administration, showing that both compounds are rapid-acting, and remained above that threshold through the final time points of 8 and 72 h. Extrapolation of the terminal elimination phase of the mean concentration-time curves was used to develop the clinical dosing frequencies of 6 to 8 h for BUP and 3.0 to 3.5 d for BSR. Some adverse effects were observed after the administration of BUP to common marmosets in this study, thus mandating judicious use in clinical practice. BSR provided a safe, long-acting option for analgesia and therefore can be used to refine analgesic protocols in this species.

Pharmacokinetics of Buprenorphine and Sustained-release Buprenorphine in Common Marmosets (Callithrix jacchus).

The use of the common marmoset monkey (Callithrix jacchus) for neuroscientific research has grown markedly in the last decade. Magnetic resonance imaging (MRI) has played a significant role in establishing the extent of comparability of marmoset brain architecture with the human brain and brains of other preclinical species (eg, macaques and rodents). As a non-invasive technique, MRI allows for the flexible acquisition of the same sequences across different species in vivo, including imaging of whole-brain functional topologies not possible with more invasive techniques. Being one of the smallest New World primates, the marmoset may be an ideal nonhuman primate species to study with MRI. As primates, marmosets have an elaborated frontal cortex with features analogous to the human brain, while also having a small enough body size to fit into powerful small-bore MRI systems typically employed for rodent imaging; these systems offer superior signal strength and resolution. Further, marmosets have a rich behavioral repertoire uniquely paired with a lissencephalic cortex (like rodents). This smooth cortical surface lends itself well to MRI and also other invasive methodologies. With the advent of transgenic modification techniques, marmosets have gained significant traction as a powerful complement to canonical mammalian modelling species. Marmosets are poised to make major contributions to preclinical investigations of the pathophysiology of human brain disorders as well as more basic mechanistic explorations of the brain. The goal of this article is to provide an overview of the practical aspects of implementing MRI and fMRI in marmosets (both under anesthesia and fully awake) and discuss the development of resources recently made available for marmoset imaging.

Magnetic Resonance Imaging of Marmoset Monkeys.

Although buprenorphine is the most frequently used opioid analgesic in common marmosets (Callithrix jacchus), there is limited information in the literature supporting current dosing regimens used for this species. The purpose of this study was to determine the pharmacokinetic profiles of single-dose buprenorphine HCl administered intramuscularly (IM) at 0.01 mg/kg in 6 adult marmosets (1.8 to 12.8 y old; 2 males, 4 females) and subcutaneously (SQ) at 0.01 mg/kg in 6 adult marmo- sets (2.3-4.4 y old; 3 males, 3 females) by mass spectrometry. Blood was collected at multiple time points from 0.25 to 24 h from unsedated animals following a hybrid sparse-serial sampling design. The maximal observed plasma concentration of buprenorphine (Cmax ) administered IM (2.57 ± 0.95 ng/mL) was significantly higher than administered SQ (1.47 ± 0.61 ng/mL). However, the time to Cmax (Tmax) was not statistically different between routes (17.4 ± 6 min for IM and 19.8 ± 7.8 min for SQ). The time of the last quantifiable concentration of buprenorphine was 5 ± 1.67 h for IM compared with 6.33 ± 1.51 h for SQ, which was not statistically different. The mean buprenorphine plasma concentration-time curves were used to propose a dosing frequency of 4 to 6 h for buprenorphine at 0.01 mg/kg IM or SQ based on a theoretical therapeutic plasma concentration threshold of 0.1 ng/mL. Based on the mean pharmacokinetic parameters and plasma-concentration time curves, both IM and SQ routes of buprenorphine at this dose provide a rapid increase in the plasma concentration of buprenorphine above the therapeutic threshold, and may be more effective for acute rather than long-lasting analgesia. Further studies are needed to examine repeated dosing regimens and the efficacy of buprenorphine in common marmosets.

Pharmacokinetics of Single-Dose Intramuscular and Subcutaneous Injections of Buprenorphine in Common Marmosets (Callithrix jacchus).

The objectives of this study were (a) to establish a population pharmacokinetic model and (b) to investigate the clinical and physiological effects of a single bolus dose of propofol in common marmosets. In Study 1, pharmacokinetic analysis was performed in six marmosets under sevoflurane anaesthesia. 8 mg/kg of propofol was administrated at a rate of 4 mg kg-1  min-1 . Blood samples were collected 2, 5, 15, 30, 60, 90, 120 or 180 min after starting propofol administration. Plasma concentration was measured, and population pharmacokinetic modelling was performed. A two-compartment model was selected as the final model. The population pharmacokinetic parameters were as follows: V1  = 1.14 L, V2  = 77.6 L, CL1  = 0.00182 L/min, CL2  = 0.0461 L/min. In Study 2, clinical and physiological parameters were assessed and recorded every 2 min after 12 mg/kg of propofol was administrated at a rate of 4 mg kg-1  min-1 . Immobilization was sustained for 5 min following propofol administration without apparent bradycardia. While combination of propofol and sevoflurane caused apnoea in Study 1, apnoea was not observed following single administration of propofol in Study 2. These data provide bases for further investigation on intravenous anaesthesia using propofol in common marmosets.

Pharmacokinetics and effects on clinical and physiological parameters following a single bolus dose of propofol in common marmosets (Callithrix jacchus).

Effects of buprenorphine, butorphanol or tramadol premedication on anaesthetic induction with alfaxalone in common marmosets (Callithrix jacchus).

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Effects of buprenorphine, butorphanol or tramadol premedication on anaesthetic induction with alfaxalone in common marmosets (Callithrix jacchus).