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Pharmacokinetics and Pharmacodynamics of Multiple Sublingual Buprenorphine Tablets in Dose‐Escalation Trials
Author(s) -
Ciraulo Domenic A.,
Hitzemann Robert J.,
Somoza Eugene,
Knapp Clifford M.,
Rotrosen John,
SaridSegal Ofra,
Ciraulo Ann Marie,
Greenblatt David J.,
Chiang C. Nora
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270005284192
Subject(s) - pharmacokinetics , pharmacodynamics , medicine , buprenorphine , pharmacology , anesthesia , opioid , receptor
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.