Pharmacokinetics of buprenorphine following intravenous and buccal administration in cats, and effects on thermal threshold

Abstract

This study reports the pharmacokinetics of buprenorphine, following i.v. and buccal administration, and the relationship between buprenorphine concentration and its effect on thermal threshold. Buprenorphine (20 μg/kg) was administered intravenously or buccally to six cats. Thermal threshold was determined, and arterial blood sampled prior to, and at various times up to 24 h following drug administration. Plasma buprenorphine concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to the time-concentration data. Pharmacokinetic/pharmacodynamic models were fitted to the concentration-thermal threshold data. Thermal threshold was significantly higher than baseline 44 min after buccal administration, and 7, 24, and 104 min after i.v. administration. A two- and three-compartment model best fitted the data following buccal and i.v. administration, respectively. Following i.v. administration, mean ± SD volume of distribution at steady-state (L/kg), clearance (mL·min/kg), and terminal half-life (h) were 11.6 ± 8.5, 23.8 ± 3.5, and 9.8 ± 3.5. Following buccal administration, absorption half-life was 23.7 ± 9.1 min, and terminal half-life was 8.9 ± 4.9 h. An effect-compartment model with a simple effect maximum model best predicted the time-course of the effect of buprenorphine on thermal threshold. Median (range) ke0 and EC50 were 0.003 (0.002-0.018)/min and 0.599 (0.073-1.628) ng/mL (i.v.), and 0.017 (0.002-0.023)/min and 0.429 (0.144-0.556) ng/mL (buccal).

Pharmacokinetic and pharmacodynamic modelling after subcutaneous, intravenous and buccal administration of a high-concentration formulation of buprenorphine in conscious cats

“…The pharmacokinetic parameters estimated in the current study are similar to those reported in the literature (Table 3) using buprenorphine in cats [9, 16, 18, 25]. Some variability exists due to different bioavailability particularly in routes other than IV.…”

“…Traditional methods used for pharmacokinetic modeling of buprenorphine in cats have studied each route of administration separately [9, 16, 18], instead of pooling data from crossover studies to strengthen estimation of parameters shared across routes of administration (CL, V1, CL2, V2). In the present study, six individuals were used in a typical cross-over design, yielding 18 related (six cats, three routes of administration) plasma concentration-time curves.…”

“…The test has been validated in free-ranging cats [7] and several studies using the TT device and evaluating the antinociceptive effects of buprenorphine have been reported in the species [3, 8–16]. The equipment was calibrated and maintained according to the manufacturer’s recommendations.…”

Pharmacokinetics of oral transmucosal and intramuscular dexmedetomidine combined with buprenorphine in cats

“…administration of buprenorphine. In agreement with our results, a comparable low bioavailability of buprenorphine following OTM administration was observed in a previous study in cats that also used LC‐MS/MS to analyse buprenorphine (Hedges et al ., ).…”

Effect of morphine, methadone, hydromorphone or oxymorphone on the thermal threshold, following intravenous or buccal administration to cats

“…), although more recent studies have found inconsistent effects and lower bioavailability than previously reported (Hedges et al. , b; Steagall et al. , ).…”