Buprenorphine assay and plasma concentration monitoring in HIV-infected substance users.
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 <or=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.
DiFrancesco
Robin
R
Pharmacotherapy Research Center, School of Pharmacy and Pharmaceutical Sciences, University at Buffalo, Buffalo, NY, USA.
Fischl
Margaret A
MA
Donnelly
Julie
J
Zingman
Barry S
BS
McCance-Katz
Elinore F
EF
Moody
David E
DE
Reichman
Richard C
RC
Gripshover
Barbara
B
Morse
Gene D
GD
D000480:Alkynes; D000069446:Atazanavir Sulfate; D048588:Benzoxazines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D001681:Biological Assay; D002047:Buprenorphine / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods; D003521:Cyclopropanes; D015658:HIV Infections / Q000097:blood* / Q000188:drug therapy; D017320:HIV Protease Inhibitors / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D015497:HIV-1; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D009292:Narcotic Antagonists / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019966:Substance-Related Disorders / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D017320:HIV Protease Inhibitors; D009292:Narcotic Antagonists; D009842:Oligopeptides; D011725:Pyridines; D002047:Buprenorphine; D000069446:Atazanavir Sulfate; C098320:efavirenz