Pharmacokinetics of Buprenorphine and Sustained Release Buprenorphine in Alpacas

Principal investigators:

Dooley, S, Aarnes, T, Bednarski, R, Lerche, P, Hubbell, J, Lakritz, J
The Ohio State University, Columbus, OH, USA

Introduction: The objective of this study was to determine pharmacokinetics of buprenorphine after IV and SC administration, and SC administration of a sustained release (SR) formulation in adult alpacas.

Methods: Buprenorphine was administered at 0.02 mg kg^-1 IV, 0.02 mg kg^-1 SC, and 0.12 mg kg^-1 SR SC to six alpacas (mean age 5.3 years, mean weight 62.7 kg, three males, and three females) with a 14-day washout in a blinded randomized trial. Twenty venous blood samples were collected over 96 hours for determination of plasma concentrations of buprenorphine, nor-buprenorphine, buprenorphine glucuronide, and nor-buprenorphine glucuronide using a validated LC-MS/MS method with LLOQ of 0.5 ng mL^-1. Pharmacokinetic parameters were calculated using non-compartmental analysis.

Results: Maximum concentrations after IV (C_p0) and SC (C_max) administration were 12.73 ng mL^-1 (range 5–22 ng mL^-1), and 1.5 ng mL^-1 (range 1.27–3.53 ng mL^-1). Clearance and steady state volumes were 45 ± 3 mL minute^-1kg^-1 and 4.7 ± 1.5 L kg^-1. Elimination half-life was 75.6 minutes ± 7.7 minutes and 122 minutes ± 62.5 minutes after IV and SC administration respectively. Bioavailability after SC administration was 64%. Concentrations after SR SC were below the limit of quantification. The metabolite buprenorphine glucuronide was detected only after IV dosing.

Conclusion: Buprenorphine has a short elimination half-life, and high clearance and steady state volume of distribution in alpacas. The SR buprenorphine or its metabolites were not detectable in plasma.