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

Abstract

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 (C_max ) administered IM (2.57 ± 0.95 ng/mL) was significantly higher than administered SQ (1.47 ± 0.61 ng/mL). However, the time to C_max (T_max) 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.

Figure 1.

Plasma concentration-time curves showing buprenorphine concentrations of individual marmosets after receiving a single injection of buprenorphine HCl (0.01 mg/kg) administered through the (A) intramuscular (IM) route (n = 6) and (C) subcutaneous (SQ) route (n = 6) up to 8 h. The time to last quantifiable plasma buprenorphine concentration (T_last) in marmosets for the IM route (B) and (D) SQ route in all marmosets. The last time point in each curve represents the last quantifiable plasma concentration in a specific marmoset.

Figure 2.

Plasma concentration-time curve showing mean plasma concentration (error bar, standard deviation) after a single intramuscular (IM) (n = 6) or subcutaneous (SQ) (n = 6) injection in marmosets up to 8 h. The hypothesized therapeutic threshold of 0.1 ng/mL is represented by the dashed line on the horizontal axis. The point at which each curve crosses this threshold is indicated by the red arrow (IM) and blue arrow (SQ).