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

J Am Assoc Lab Anim Sci. 2021 Mar 1;60(2):188-194. doi: 10.30802/AALAS-JAALAS-20-000082. Epub 2020 Dec 29.

Abstract

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.

Publication types

  • Randomized Controlled Trial, Veterinary
  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / pharmacokinetics*
  • Animals
  • Area Under Curve
  • Buprenorphine / administration & dosage
  • Buprenorphine / pharmacokinetics*
  • Callithrix / metabolism*
  • Delayed-Action Preparations / administration & dosage
  • Female
  • Half-Life
  • Male

Substances

  • Analgesics, Opioid
  • Delayed-Action Preparations
  • Buprenorphine