OBJECTIVE To determine pharmacokinetics and sedative effects of buprenorphine after IV and oral transmucosal (OTM) administration in guinea pigs. ANIMALS 14 male guinea pigs (6 adults for preliminary experiment; eight 8 to 11-week-old animals for primary study). PROCEDURES A preliminary experiment was conducted to determine an appropriate buprenorphine dose. In the primary study, buprenorphine (0.2 mg/kg) was administered IV or OTM, and blood samples were obtained. The pH of the oral cavity was measured before OTM administration. Sedation was scored for 6 hours on a scale of 0 to 3 (0 = no sedation and 3 = heavy sedation). After a 7-day washout period, procedures were repeated in a crossover manner. Plasma buprenorphine concentration was quantified, and data were analyzed with a noncompartmental pharmacokinetic approach. RESULTS Mean peak plasma buprenorphine concentrations were 46.7 and 2.4 ng/mL after IV and OTM administration, respectively. Mean time to maximum plasma buprenorphine concentration was 1.5 and 71.2 minutes, and mean terminal half-life was 184.9 and 173.0 minutes for IV and OTM administration, respectively. There was a range of sedation effects (0 to 2) for both routes of administration, which resolved within the 6-hour time frame. CONCLUSIONS AND CLINICAL RELEVANCE On the basis of pharmacokinetic parameters for this study, buprenorphine at 0.2 mg/kg may be administered IV every 7 hours or OTM every 4 hours to maintain a target plasma concentration of 1 ng/mL. Further studies are needed to evaluate administration of multiple doses and sedative effects in guinea pigs with signs of pain.