Show simple item record

dc.contributor.authorKuhlman, James John, Jr.
dc.date.accessioned2012-04-20T19:27:17Z
dc.date.available2012-04-20T19:27:17Z
dc.date.issued1996
dc.identifier.urihttp://hdl.handle.net/10713/1466
dc.descriptionUniversity of Maryland, Baltimore. Toxicology. Ph.D. 1996en_US
dc.description.abstractSuccess or failure of treatment for opioid dependence can be affected by the plasma concentration of the therapeutic agent. Measuring plasma concentrations allows dosages to be individualized and therapeutic failures to be investigated. The high potency and lipophilicity of buprenorphine produce low plasma concentrations making measurement difficult. Buprenorphine plasma concentrations have been measured most often using radioimmunoassay which cross reacts with buprenorphine glucuronide and its N-dealkyl metabolite, norbuprenorphine.;The goals of this study were to develop a sensitive, specific method to measure buprenorphine and norbuprenorphine in plasma; to investigate buprenorphine pharmacokinetics by different routes of administration; and to measure steady-state plasma concentrations following daily and alternate day dosing during chronic opioid maintenance therapy. Buprenorphine and norbuprenorphine were measured simultaneously with negative chemical ionization tandem mass spectrometry. Plasma samples were extracted by solid phase extraction columns and heptafluorobutyryl derivatives were formed to enhance sensitivity. Limits of detection for buprenorphine and norbuprenorphine were 0.15 ng/mL and 0.016 ng/mL, respectively. Linearity, limits of detection and limits of quantitation for both compounds were sufficient for measuring plasma concentrations found during buprenorphine maintenance pharmacotherapy. Buprenorphine pharmacokinetics were determined for intravenous, sublingual and buccal administration. Sublingual administration was more efficient than buccal administration resulting in 51.4% bioavailability versus 27.8% for buccal administration. Sublingual peak buprenorphine plasma concentration following a 4.0 mg dose was 3.31 ng/mL at 0.71 hours. The maximum norbuprenorphine plasma concentration was 0.41 ng/mL. The intravenous elimination half-life agreed with previous analgesic dose studies, but the sublingual and buccal elimination half-lives were considerably longer than the intravenous elimination half-life. Eleven heroin dependent subjects were administered sublingual buprenorphine either daily or every other day over 36 days. Withdrawal scores and pupil diameter were collected along with plasma samples. Trough steady-state buprenorphine plasma concentration following daily 8 mg doses was 0.87 ng/mL and was associated with low withdrawal scores. Alternate day dosing produced lower plasma concentrations and higher withdrawal scores. The subjects' buprenorphine dosage was abruptly substituted with placebo administrations on day 37. The terminal elimination half-life following the chronic 8 mg sublingual dosing was 42 hours.en_US
dc.language.isoen_USen_US
dc.subjectHealth Sciences, Toxicologyen_US
dc.subjectHealth Sciences, Pharmacologyen_US
dc.subjectChemistry, Analyticalen_US
dc.titleAn investigation of buprenorphine and norbuprenorphine plasma concentrations in opioid dependence therapy: Analysis, pharmacokinetics and chronic administrationen_US
dc.typedissertationen_US
dc.contributor.advisorLevine, Barry, 1957-
dc.contributor.advisorCone, Edward J.
dc.identifier.ispublishedYes
 Find Full text

This item appears in the following Collection(s)

Show simple item record