buprenorphine and efavirenz

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

Topics: Alkynes; Atazanavir Sulfate; Benzoxazines; Biological Assay; Buprenorphine; Calibration; Chromatography, Liquid; Cyclopropanes; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Mass Spectrometry; Molecular Structure; Narcotic Antagonists; Oligopeptides; Pyridines; Reproducibility of Results; Sensitivity and Specificity; Substance-Related Disorders; Tandem Mass Spectrometry

This study examined drug interactions between buprenorphine, an opioid partial agonist medication used in the treatment of opioid dependence, and the nonnucleoside reverse-transcriptase inhibitors (NNRTIs) efavirenz (EFV) and delavirdine (DLV). Opioid-dependent, buprenorphine/naloxone-maintained, human immunodeficiency virus (HIV)-negative volunteers (n=10 per NNRTI) participated in 24-h sessions to determine pharmacokinetics of buprenorphine and of buprenorphine with either EFV or DLV after administration of standard doses of either antiretroviral for 15 or 7 days, respectively. Opiate withdrawal symptoms, cognitive effects, and adverse events were determined before and after antiretroviral administration in opioid-dependent participants. The pharmacokinetics of NNRTIs in healthy control participants were used to determine the effect of buprenorphine on NNRTIs. EFV decreased the buprenorphine area under the concentration-time curve (P<.001). DLV increased buprenorphine concentrations (P<.001). Clinically significant consequences of these interactions were not observed. Buprenorphine did not alter antiretroviral pharmacokinetics. Adjustments of doses of either buprenorphine or EFV or DLV are not likely to be necessary when these drugs are administered for the treatment of opiate dependence and HIV disease.

Topics: Adult; Alkynes; Area Under Curve; Benzoxazines; Buprenorphine; Case-Control Studies; Cohort Studies; Cyclopropanes; Delavirdine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Interactions; Female; HIV Infections; Humans; Male; Narcotic Antagonists; Opioid-Related Disorders; Oxazines; Probability; Prognosis; Reference Values; Reverse Transcriptase Inhibitors; Risk Assessment; Statistics, Nonparametric; Treatment Outcome