Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine tablets in dose-escalation trials

J Clin Pharmacol. 2006 Feb;46(2):179-92. doi: 10.1177/0091270005284192.

Abstract

In this investigation, the pharmacokinetic and pharmacodynamic properties were determined of multiple doses of sublingual tablets containing either buprenorphine alone or buprenorphine and naloxone. Subjects were experienced opiate users who received escalating doses (4-24 mg) of buprenorphine either alone or in combination with naloxone. Peak concentration (Cmax) and area under the concentration-time curves (AUCs) increased for both buprenorphine and naloxone with escalating doses. Significant differences were found across the range of doses administered for dose-adjusted Cmax for both tablet formulations and for the dose-adjusted AUCs for the buprenorphine-naloxone tablets. For both formulations, the maximal buprenorphine-induced decreases in respiratory rate and pupil diameter did not vary significantly across doses. Several of the subjective effects of buprenorphine did not increase as the dose of buprenorphine administered was increased. These findings are consistent with the ceiling effect associated with the partial agonist actions of buprenorphine. They also indicate a lack of dose proportionality for buprenorphine sublingual tablets, at least during the times at which levels of this agent are highest.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Administration, Sublingual
  • Adult
  • Area Under Curve
  • Blood Pressure / drug effects
  • Buprenorphine / administration & dosage
  • Buprenorphine / pharmacokinetics*
  • Buprenorphine / pharmacology*
  • Chromatography, High Pressure Liquid
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Female
  • Heart Rate / drug effects
  • Humans
  • Male
  • Naloxone / administration & dosage
  • Naloxone / pharmacokinetics
  • Narcotic Antagonists / administration & dosage
  • Narcotic Antagonists / pharmacokinetics*
  • Narcotic Antagonists / pharmacology*
  • Pupil / drug effects
  • Respiratory Mechanics / drug effects

Substances

  • Drug Combinations
  • Narcotic Antagonists
  • Naloxone
  • Buprenorphine