Pharmacokinetics of buprenorphine following intravenous administration in dogs

Objective-To determine pharmacokinetics of buprenorphine in dogs after IV administration. Animals-6 healthy adult dogs. Procedures-6 dogs received buprenorphine at 0.015 mg/kg, IV. Blood samples were collected at time 0 prior to drug administration and at 2, 5, 10, 15, 20, 30, 40, 60, 90, 120, 180, 240, 360, 540, 720, 1,080, and 1,440 minutes after drug administration. Serum buprenorphine concentrations were determined by use of double-antibody radioimmunoassay. Data were subjected to noncompartmental analysis with area under the time-concentration curve to infinity (AUC) and area under the first moment curve calculated to infinity by use of a log-linear trapezoidal model. Other kinetic variables included terminal rate constant (k(el)) and elimination half-life (t1/2), plasma clearance (CI), volume of distribution at steady state (Vd(ss)), and mean residence time (MRT). Time to maximal concentration (T-max) and maximal serum concentration (C-max) were measured. Results-Median (range) values for T-max and MRT were 2 minutes (2 to 5 minutes) and 264 minutes (199 to 600 minutes), respectively. Harmonic mean and pseudo SD for t1/2 were 270 +/- 130 minutes; mean +/- SD values for remaining pharmacokinetic variables were as follows: C-max 14 +/- 2.6 ng/mL; AUC, 3,082 +/- 1,047 ng.min/mL; Vd(ss), 1.59 +/- 0.285 L/kg; CI, 5.4 +/- 1.9 mL/min/kg; and, k(el), 0.0026 +/- 0.0012. Conclusions and Clinical Relevance-Pharmacokinetic variables of buprenorphine reported here differed from those previously reported for dogs. Wide variations in individual t1/2 values suggested that dosing intervals be based on assessment of pain status rather than prescribed dosing intervals.