Interaction between buprenorphine and atazanavir or atazanavir/ritonavir

Abstract

Opioid addiction and HIV disease frequently co-occur. Adverse drug interactions have been reported between methadone and some HIV medications, but less is known about interactions between buprenorphine, an opioid partial agonist used to treat opioid dependence, and HIV therapeutics. This study examined drug interactions between buprenorphine and the protease inhibitors atazanavir and atazanavir/ritonavir. Opioid-dependent, buprenorphine/naloxonemaintained, HIV-negative volunteers (n=10 per protease inhibitor) participated in two 24-hour sessions to determine pharmacokinetics of (1) buprenorphine and (2) buprenorphine and atazanavir (400 mg daily) or atazanavir/ritonavir (300/100 mg daily) following administration for 5 days. Objective opiate withdrawal scale scores and Mini-Mental State Examination were determined prior to and following antiretroviral administration to examine pharmacodynamic effects. Pharmacokinetics of atazanavir and atazanavir/ritonavir were compared in subjects and matched, healthy controls (n=10 per protease inhibitor) to determine effects of buprenorphine. With atazanavir and atazanavir/ritonavir, respectively concentrations of buprenorphine (p<0.001, p<0.001), norbuprenorphine (p=0.026, p=0.006), buprenorphine glucuronide (p=0.002, p<0.001), and norbuprenorphine glucuronide (NS, p=0.037) increased. Buprenorphine treatment did not significantly alter atazanavir or ritonavir concentrations. Three buprenorphine/naloxonemaintained participants reported increased sedation with atazanavir/ritonavir. Atazanavir or atazanavir/ritonavir may increase buprenorphine and buprenorphine metabolite concentrations and might require a decreased buprenorphine dose.

P-Glycoprotein Is a Major Determinant of Norbuprenorphine Brain Exposure and Antinociception

“…If, however, these are clinically relevant, then findings described in this article may explain, in part, clinical observations about buprenorphine (Bruce and Altice, 2006;McCance-Katz et al, 2007). Atazanavir and atazanavir/ ritonavir increased plasma buprenorphine and norbuprenorphine concentrations 1.3-to 2.5-fold, albeit not into ranges shown previously to cause side effects (McCance-Katz et al, 2007).…”

Atazanavir plasma concentrations are impaired in HIV-1-infected adults simultaneously taking a methadone oral solution in a once-daily observed therapy setting

“…This usage is supported by its combinability with once-daily nucleoside/ nucleotide reverse transcriptase inhibitors, such as tenofovir-DF [19] and emtricitabine. The substitute opiate buprenorphine [4,12] can also be co-administered without altering the pharmacokinetics of atazanavir/ritonavir. However, the cases of patients reported here show that the intake of oral methadone solution may have an impact on the pharmacokinetic parameters of ritonavir-boosted atazanavir.…”

<i>C</i>-Homomorphinan Derivatives as Lead Compounds to Obtain Safer and More Clinically Useful Analgesics

“…The combined organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure. Purification with preparative TLC (saturated ammonia-chloroform-methanol=50 : 1) gave the title compound (15 Binding Assays The human μ, δ, or κ opioid receptor recombinant CHO cell pellets were resuspended in 50 mM Tris-HCl buffer containing 5 mM MgCl 2 , 1 mM ethylene glycol bis(2-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), pH 7.4. The cell suspensions were disrupted by use of a glassteflon homogeniser and centrifuged at 48000×g for 15 min.…”

“…14) While buprenorphine has the aforementioned advantages, there still is room for improvement in clinical utility due to the limitations of this drug. For example, since buprenorphine is metabolized by CYP3A4, a CYP isozyme involved in metabolism of a wide variety of medicines, buprenorphine occasionally received the effects of a drug-drug interaction with some medicines such as anti-human immunodeficiency virus (HIV) drugs (protease inhibitors), 15) benzodiazepines, 16) and azole antifungals. 17,18) Additionally, buprenorphine is hardly administered orally because it extensively suffers from a first pass effect.…”