TY - JOUR
T1 - Buprenorphine assay and plasma concentration monitoring in HIV-infected substance users
AU - DiFrancesco, Robin
AU - Fischl, Margaret A.
AU - Donnelly, Julie
AU - Zingman, Barry S.
AU - McCance-Katz, Elinore F.
AU - Moody, David E.
AU - Reichman, Richard C.
AU - Gripshover, Barbara
AU - Morse, Gene D.
N1 - Funding Information:
The technical support of Colleen Hagler, Linda Hale, Jill Hochreitter and Jill Lapham is greatly appreciated. The contributions of Raju Sadal, Julie Sarlo, Carol Greisberger, Leslie Thompson, Jenna Thomas and the clinical research staff at the Montefiore Medical Center AIDS Center, the University of Rochester HIV Program, the University of Miami AIDS Research Unit, and the University Hospitals Case Medical Center HIV Program and the patients at each of the participating HIV treatment centers is appreciated. This research was supported by grant # DA015024 (GDM), DA13004 (EMK), DA10100 (DEM), administrative supplement 3R01DA015024-03S2 from the National Institute on Drug Abuse, NIH Shared Instrument Grant #SIORRR14572 and support from the Kapoor Foundation. Dr. Zingman is supported in part by the Center for AIDS Research at the Albert Einstein College of Medicine and Montefiore Medical Center (NIH AI-51519).
PY - 2007/5/9
Y1 - 2007/5/9
N2 - 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.
AB - 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.
KW - Antiretrovirals
KW - Buprenorphine
KW - HIV
KW - Plasma concentration monitoring
KW - Substance abuse treatment
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U2 - 10.1016/j.jpba.2007.02.014
DO - 10.1016/j.jpba.2007.02.014
M3 - Article
C2 - 17391891
AN - SCOPUS:34047260735
SN - 0731-7085
VL - 44
SP - 188
EP - 195
JO - Journal of Pharmaceutical and Biomedical Analysis
JF - Journal of Pharmaceutical and Biomedical Analysis
IS - 1
ER -