Pharmacokinetics, bioavailability and opioid effects of liquid versus tablet buprenorphine.
OBJECTIVE
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.


METHODS
Randomized, open-label, two-way crossover study.


METHODS
Inpatient hospitalization for 21 days.


METHODS
Twenty-four male and females in general good health and meeting DSM-IV criteria for opiate dependence.


METHODS
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.


METHODS
Pharmacokinetic analyses, opiate effects and adverse events.


RESULTS
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.
Compton
Peggy
P
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
Ling
Walter
W
Moody
David
D
Chiang
Nora
N
D000328:Adult; D001682:Biological Availability; D002047:Buprenorphine / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004304:Dosage Forms; D004333:Drug Administration Routes; D005260:Female; D006801:Humans; D008297:Male; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D009293:Opioid-Related Disorders / Q000188:drug therapy*
D004304:Dosage Forms; D009292:Narcotic Antagonists; D002047:Buprenorphine