Source
School of Nursing, University of California at Los Angeles, Factor Building 4-246, Box 956918, Los Angeles, CA 90095-6918, USA. pcompton@sonnet.ucla.edu
Abstract
AIMS:
Two tablet formulations of buprenorphine (a buprenorphine mono-product, Subutex, and a buprenorphine/naloxone combination product, Suboxone) are available for use in the treatment of opioid addiction; however, the bulk of the clinical studies supporting its approval by the US Food and Drug Administration (FDA) were conducted with a sublingual liquid preparation. To assist the clinician in interpreting the relevant literature in establishing dosing parameters for prescription of tablet buprenorphine, this study was designed to compare the steady state: (1) pharmacokinetics and bioavailability, and (2) physiological, subjective and objective opiate effects of two 8 mg buprenorphine tablets (16 mg) to those of 1 ml (8 mg/ml) buprenorphine solution based upon early reports suggesting that the bioavailability of the tablet was approximately 50% of that of the liquid.
DESIGN:
Randomized, open-label, two-way crossover study.
SETTING:
Inpatient hospitalization for 21 days.
PARTICIPANTS:
Twenty-four male and females in general good health and meeting DSM-IV criteria for opiate dependence.
INTERVENTION:
Subjects received one of the two buprenorphine formulations in the first 10-day period, and the other for the second 10-day period with no washout.
MEASUREMENTS:
Pharmacokinetic analyses, opiate effects and adverse events.
FINDINGS:
Drug steady state was reached by Day 7 of each 10-day period, area under the curve for 16 mg (two 8 mg) tablets was higher than the solution. The only non-kinetic statistically significant difference observed between the formulations was in changes in total opioid agonist score.
CONCLUSIONS:
The serum concentration achieved by 16 mg of tablet buprenorphine is higher than that of the 8 mg solution, although differences between physiologic, subjective and objective opioid effects were not noted. The relative bioavailability of tablet versus solution is estimated to be 0.71; thus, with respect to dosing parameters for the tablet, clinicians should consider using less than 16 mg to achieve bioequivalence to the 8 mg solution.