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

Domenic A. Ciraulo, Robert J. Hitzemann, Eugene Somoza, Clifford M. Knapp, John Rotrosen, Ofra Sarid-Segal, Ann Marie Ciraulo, David J. Greenblatt, C. Nora Chiang

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)179-192
Number of pages14
JournalJournal of Clinical Pharmacology
Issue number2
StatePublished - Feb 2006
Externally publishedYes


  • Naloxone
  • Opioid dependence
  • Partial agonist
  • Sublingual

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


Dive into the research topics of 'Pharmacokinetics and pharmacodynamics of multiple sublingual buprenorphine tablets in dose-escalation trials'. Together they form a unique fingerprint.

Cite this