Sublingual buprenorphine formulations have been developed as treatments for opioid dependence. In three studies, opioid naive healthy male subjects received Subutex(R) tablets (buprenorphine 2 and 8 mg [N=27] or 12 and 16 mg [N=27]) or Suboxone(R) (two formulations) tablets (buprenorphine 8 mg/naloxone 2 mg [N=36]) sublingually, under a naltrexone block for assessment of buprenorphine pharmacokinetics and tablet disintegration times. Plasma buprenorphine was quantified up to 72 h post-dose using a sensitive LC-MS/MS assay. Mean C m a x values ranged from 1.6 to 6.4 ng/ml and t m a x from 0.5 to 3 h. Concentrations declined bi-exponentially and fluctuations after a meal suggested enterohepatic recirculation of buprenorphine. The terminal half-life was approximately 26 h (range 9-69). C m a x and AUC appeared to increase in proportion to Subutex(R) dose over 8-16 mg. The Suboxone(R) formulations were bioequivalent. The least squares mean (90% CI) treatment ratio for C m a x was 1.00 (0.92-1.10) and AUC was 1.00 (0.95-1.06). Median times of disintegration were similar for all doses and formulations (range 6-12 min). Sublingual buprenorphine, up to 40 times the 400 μg analgesic dose, was well tolerated in these opioid naive subjects, as administration of naltrexone 50-150 mg was sufficient to attenuate anticipated adverse effects in this population of subjects.