Tipranavir/Ritonavir Induction of Buprenorphine Glucuronide Metabolism in HIV-Negative Subjects Chronically Receiving Buprenorphine/Naloxone

Bruce, R. Douglas; Moody, David E.; Fang, Wenfang B.; Chodkowski, Diane; Andrews, Laurie; Friedland, Gerald

doi:10.3109/00952990.2011.568081

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…Tipranavir significantly altered the disposition of norbuprenorphine without producing a pharmacodynamic effect [184]. This reduction in norbuprenorphine concentrations is suggestive of a combined inhibition of the UGT 1A family and CYP 3A4 that spares UGT 2B7 leading to a shunting of buprenorphine away from the production of norbuprenorphine and towards buprenorphine-3-glucuronide [185]. …”

Section: Interactions Between Buprenorphine and Specific Antiretrovirmentioning

confidence: 99%

“…The increase in buprenorphine and the reduction in norbuprenorphine are reminiscent of the tipranavir/ritonavir inhibition of 3A4 and the shunting of buprenorphine metabolism away from norbuprenorphine. [185]. Based on this data, boceprevir can be safely dosed in patients on methadone or buprenorphine.…”

Section: Interactions Between Hepatitis C Antivirals and Methadone Ormentioning

confidence: 99%

See 1 more Smart Citation

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

Bruce

Moody

Altice

et al. 2013

Expert Review of Clinical Pharmacology

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Global access to opioid agonist therapy and HIV/HCV treatment is expanding but when used concurrently, problematic pharmacokinetic and pharmacodynamic interactions may occur. Review of articles from 1966 into 2012 in Medline using the following keywords: HIV, AIDS, HIV therapy, HCV, HCV therapy, antiretroviral therapy, HAART, drug interactions, methadone, and buprenorphine. Additionally, abstracts from national and international meetings and a review of conference proceedings were conducted; selected reports were reviewed as well. The metabolism of both opioid and antiretroviral therapies, description of their known interactions, and clinical implications and management of these interactions are reviewed. Important pharmacokinetic and pharmacodynamic drug interactions affecting either methadone or HIV medications have been demonstrated within each class of antiretroviral agents. Drug interactions between methadone, buprenorphine and HIV medications are known and may have important clinical consequences. Clinicians must be alert to these interactions and have a basic knowledge regarding their management.

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Section: Interactions Between Buprenorphine and Specific Antiretrovirmentioning

confidence: 99%

Section: Interactions Between Hepatitis C Antivirals and Methadone Ormentioning

confidence: 99%

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

Bruce

Moody

Altice

et al. 2013

Expert Review of Clinical Pharmacology

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“…The lack of an interaction between fenofibrate and lopinavir‐ritonavir and between fenofibrate and ritonavir is likely explained by fenofibric acid being largely glucuronidated by UGT2B7, which does not appear to undergo induction by ritonavir, despite ritonavir's ability to modulate the activity of other UGT enzymes such as UGT1A1 and UGT1A4 . Additionally, in contrast to the reduction in gemfibrozil absorption that was previously observed with concurrent administration of lopinavir‐ritonavir, neither lopinavir‐ritonavir nor ritonavir alone significantly affected fenofibric acid absorption in the current investigation.…”

Section: Discussionmentioning

confidence: 85%

“…Lopinavir‐ritonavir and ritonavir alone were chosen for coadministration with fenofibrate in this study based on the previously described interaction between lopinavir‐ritonavir and gemfibrozil (a fibric acid derivative that is chemically similar to fenofibrate) and because fenofibric acid is largely biotransformed through glucuronidation and several glucuronidation pathways are known to undergo induction in the presence of ritonavir and/or lopinavir‐ritonavir . In addition, although lopinavir‐ritonavir is no longer considered a recommended protease inhibitor for inclusion in cART regimens, it continues to be a widely used protease inhibitor throughout the world and therefore remains clinically relevant .…”

Section: Discussionmentioning

confidence: 99%

Lack of an Effect of Ritonavir Alone and Lopinavir-Ritonavir on the Pharmacokinetics of Fenofibric Acid in Healthy Volunteers

et al. 2016

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Study Objective As we previously observed a significant 41% reduction in gemfibrozil exposure after 2 weeks of lopinavir-ritonavir administration, we sought to determine the influence of lopinavir-ritonavir and ritonavir alone on the pharmacokinetics of fenofibric acid, an alternative to gemfibrozil for the treatment of elevated triglyceride levels. Design Open-label, single-sequence pharmacokinetic study. Setting Clinical Research Center at the National Institutes of Health. Subjects Thirteen healthy adult volunteers. Intervention Subjects received a single oral dose of fenofibrate 145 mg during three study phases: before ritonavir administration, after 2 weeks of administration of ritonavir 100 mg twice daily, and after 2 weeks of administration of lopinavir 400 mg–ritonavir 100 mg twice daily. Measurements and Main Results Serial blood samples were collected over 120 hours for determination of fenofibric acid concentrations. Fenofibric acid pharmacokinetic parameter values were compared before and after concomitant ritonavir or lopinavir-ritonavir administration. The geometric mean ratios (90% confidence intervals) for fenofibric acid area under the plasma concentration–time curve were 0.89 (0.77–1.01) after 14 days of ritonavir alone compared with baseline (p>0.05) and 0.87 (0.69–1.05) after 14 days of lopinavir-ritonavir compared with baseline (p>0.05). Study drugs were generally well tolerated; all adverse events were mild or moderate, transient, and resolved without intervention. Conclusion In contrast to a significant interaction between gemfibrozil and lopinavir-ritonavir, neither lopinavir-ritonavir nor ritonavir alone altered the pharmacokinetics of fenofibric acid in healthy volunteers. These data suggest that fenofibrate remains an important option in human immunodeficiency virus–infected patients receiving common ritonavir-boosted therapy.

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“…As such, studies have shown a statistically significant increase in buprenorphine plasma levels in subjects concomitantly administered buprenorphine and ART regimens involving ritonavir. [249][250][251][252] This type of DDI increases the risk of buprenorphine toxicity and can create the potential for opioid excess. Despite this risk, subjects in these studies did not show any signs of opioid excess or withdrawal 198,212,[249][250][251][252][253] (Table S6).…”

Section: Buprenorphinementioning

confidence: 99%

Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs

2018

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Psychotropic medications are frequently co-prescribed with antiretroviral therapy (ART), owing to a high prevalence of psychiatric illness within the population living with HIV, as well as a 7-fold increased risk of HIV infection among patients with psychiatric illness. While ART has been notoriously associated with a multitude of pharmacokinetic drug interactions involving the cytochrome P450 enzyme system, the magnitude and clinical impact of these interactions with psychotropics may range from negligible effects on plasma concentrations to life-threatening torsades de pointes or respiratory depression. This comprehensive review summarizes the currently available information regarding drug–drug interactions between antiretrovirals and pharmacologic agents utilized in the treatment of psychiatric disorders—antidepressants, stimulants, antipsychotics, anxiolytics, mood stabilizers, and treatments for opioid use disorder and alcohol use disorder—and provides recommendations for their management. Additionally, overlapping toxicities between antiretrovirals and the psychotropic classes are highlighted. Knowledge of the interaction and adverse effect potential of specific antiretrovirals and psychotropics will allow clinicians to make informed prescribing decisions to better promote the health and wellness of this high-risk population.

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Tipranavir/Ritonavir Induction of Buprenorphine Glucuronide Metabolism in HIV-Negative Subjects Chronically Receiving Buprenorphine/Naloxone

Cited by 8 publications

References 23 publications

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

A review of pharmacological interactions between HIV or hepatitis C virus medications and opioid agonist therapy: implications and management for clinical practice

Lack of an Effect of Ritonavir Alone and Lopinavir-Ritonavir on the Pharmacokinetics of Fenofibric Acid in Healthy Volunteers

Drug–drug interactions and clinical considerations with co-administration of antiretrovirals and psychotropic drugs

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