Buprenorphine assay and plasma concentration monitoring in HIV-infected substance users

Robin DiFrancesco, Margaret A. Fischl, Julie Donnelly, Barry S. Zingman, Elinore F. McCance-Katz, David E. Moody, Richard C. Reichman, Barbara Gripshover, Gene D. Morse

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The availability of buprenorphine (BUP) provides an alternative approach to the treatment of opioid addiction with methadone, an agent that has many drug-drug interactions when combined with antiretroviral therapy (ART). However, due to limited long-term pharmacokinetic studies in HIV-infected patients, the clinical use of BUP, a CYP450-3A4 substrate, will require that studies be conducted to examine safety, tolerability and pharmacokinetics when these drugs are taken for chronic treatment. One clinical approach could include plasma concentration monitoring to avoid under- or overdosing BUP secondary to drug interactions with ART. The measurement of BUP and its active metabolite, norbuprenorphine (NBUP) facilitates the addition of BUP to ART in an attempt to avoid drug toxicity as described in a recent report by Bruce et al. Therefore, our objective was to validate a BUP assay and integrate its application into an ongoing antiretroviral (ARV) plasma concentration monitoring program. A chromatographic method for monitoring BUP and its active metabolite, NBUP was investigated. An assay was developed that would facilitate BUP and ARV measurement from a single 3 mL blood sample (0.75 mL plasma required) in conjunction with a previously validated multiple ARV HPLC method. The method measures BUP and NBUP over the range from 0.25 to 50 ng/mL with mass spectrometry detection. Inter- and intra-assay variation was ≤11%, across the concentration range. The method quantitates BUP and NBUP plasma concentrations within the range of expected values from current BUP dosing guidelines. Use of this combined BUP and ARV plasma concentration monitoring approach for a representative patient receiving BUP, atazanavir and efavirenz demonstrated its clinical application.

Original languageEnglish (US)
Pages (from-to)188-195
Number of pages8
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume44
Issue number1
DOIs
StatePublished - May 9 2007

Keywords

  • Antiretrovirals
  • Buprenorphine
  • HIV
  • Plasma concentration monitoring
  • Substance abuse treatment

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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