Bioavailability of sublingual buprenorphine.
Buprenorphine administered sublingually is a promising treatment for opiate dependence. Utilizing a new, sensitive, and specific gas chromatographic electron-capture detector assay, the absolute bioavailability of sublingual buprenorphine was determined in six healthy volunteers by comparing plasma concentrations after 3- and 5-minute exposures to 2 mg sublingual and 1 mg intravenous buprenorphine. The amount of unabsorbed buprenorphine in saliva was measured after 2-, 4-, and 10-minute exposures to 2 mg sublingual buprenorphine in 12 participants. Pharmacokinetic parameters were analyzed by analysis of variance; bioequivalence was evaluated by the Schuirmann two-sided test. The 3- and 5-minute sublingual exposures each allowed 29 +/- 10% bioavailability (area under the plasma concentration-time curve unextrapolated) and were bioequivalent. Buprenorphine recovered from saliva after 2-, 4-, and 10-minute exposures was, on average, 52% to 55% of dose. Increased saliva pH was correlated with decreased recovery from saliva. Study results indicate that bioavailability of sublingual buprenorphine is approximately 30%. Sublingual exposure times between 3 and 5 minutes produce equivalent results. Buprenorphine remaining in saliva causes an almost twofold overestimation of bioavailability.
Mendelson
J
J
Drug Dependence Research Center, Langley Porter Psychiatric Institute, University of California, San Francisco 94143-0984, USA.
Upton
R A
RA
Everhart
E T
ET
Jacob
P
P
Jones
R T
RT
D000286:Administration, Sublingual; D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000704:Analysis of Variance; D001682:Biological Availability; D002047:Buprenorphine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009293:Opioid-Related Disorders / Q000517:prevention & control*; D012463:Saliva
D000701:Analgesics, Opioid; D002047:Buprenorphine