Clinical pharmacology of buprenorphine: Ceiling effects at high doses

Sharon L. Walsh, Kenzie L. Preston, Maxine L Stitzer, Edward J. Cone, George Bigelow

Research output: Contribution to journalArticle

Abstract

Objective: The purpose of this study was to characterize the acute effects of buprenorphine, an opioid partial μ-agonist, across a wide range of doses in comparison to methadone. Method: Healthy adult male volunteers, who had experience with but were not physically dependent on opioids, participated while residing on a closed research unit. Four subjects received buprenorphine (0, 1, 2, 4, 8, 16, and 32 mg sublingually and five subjects received methadone (0, 15, 30, 45, and 60 mg orally) in ascending order at 1-week intervals. Physiologic, subjective, and behavioral measures were monitored for 96 hours after drug administration. Results: Both drugs produced typical opioid agonist effects (positive mood, sedation, respiratory depression, and miosis), some of which persisted for 24 to 48 hours. A plateau was observed for the dose effects of buprenorphine on subjective measures and respiratory depression. Pharmacokinetic data revealed that plasma concentrations of buprenorphine were linearly related to dose, indicating no limits on sublingual absorption in this dose range. Conclusions: This study shows a plateau on buprenorphine effects, consistent with its partial agonist classification, and that single doses of buprenorphine up to 70 times the recommended analgesic dose are well tolerated by nondependent humans.

Original languageEnglish (US)
Pages (from-to)569-580
Number of pages12
JournalClinical Pharmacology and Therapeutics
Volume55
Issue number5
StatePublished - May 1994

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Buprenorphine
Clinical Pharmacology
Opioid Analgesics
Methadone
Respiratory Insufficiency
Miosis
Pharmaceutical Preparations
Analgesics
Volunteers
Pharmacokinetics
Research

ASJC Scopus subject areas

  • Pharmacology

Cite this

Clinical pharmacology of buprenorphine : Ceiling effects at high doses. / Walsh, Sharon L.; Preston, Kenzie L.; Stitzer, Maxine L; Cone, Edward J.; Bigelow, George.

In: Clinical Pharmacology and Therapeutics, Vol. 55, No. 5, 05.1994, p. 569-580.

Research output: Contribution to journalArticle

Walsh, Sharon L. ; Preston, Kenzie L. ; Stitzer, Maxine L ; Cone, Edward J. ; Bigelow, George. / Clinical pharmacology of buprenorphine : Ceiling effects at high doses. In: Clinical Pharmacology and Therapeutics. 1994 ; Vol. 55, No. 5. pp. 569-580.
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