alexa Unexpected drug-drug interactions in human immunodeficiency virus (HIV) therapy: induction of UGT1A1 and bile efflux transporters by Efavirenz.
Infectious Diseases

Infectious Diseases

Journal of AIDS & Clinical Research

Author(s): Lee LS, Pham P, Flexner C

Abstract Share this page

Abstract INTRODUCTION: Efavirenz is an inducer of drug metabolism enzymes. We studied the effect of efavirenz and ritonavir-boosted darunavir on serum unconjugated and conjugated bilirubin, as probes for UGT1A1 and bile transporters. MATERIALS AND METHODS: Healthy volunteers were enrolled in a clinical trial. There were 3 periods: Period 1, 10 days of darunavir 900 mg with ritonavir 100 mg once daily; Period 2, 14 days of efavirenz 600 mg with darunavir/ritonavir once daily; and Period 3, 14 days of efavirenz 600 mg once daily. Serum bilirubin (conjugated and unconjugated) concentrations were obtained at baseline, at the end of each phase and at exit. RESULTS: We recruited 7 males and 5 females. One subject developed grade 3 hepatitis on efavirenz and was excluded. Mean serum unconjugated bilirubin concentrations were 6.09 μmol/L (95\% confidence interval [CI], 4.99 to 7.19) at baseline, 5.82 (95\% CI, 4.88 to 6.76) after darunavir/ritonavir, 4.00 (95\% CI, 2.92 to 5.08) after darunavir/ritonavir with efavirenz, 3.55 (95\% CI, 2.58 to 4.51) after efavirenz alone and 5.27 (95\% CI, 3.10 to 7.44) at exit (P <0.01 for the efavirenz phases). Mean serum conjugated bilirubin concentrations were 3.55 μmol/L (95\% CI, 2.73 to 4.36) at baseline, 3.73 (95\% CI, 2.77 to 4.68) after darunavir/ritonavir, 2.91 (95\% CI, 2.04 to 3.78) after darunavir/ritonavir with efavirenz, 2.64 (95\% CI, 1.95 to 3.33) after efavirenz alone and 3.55 (95\% CI, 2.19 to 4.90) at exit (P <0.05 for the efavirenz phases). CONCLUSION: Efavirenz decreased unconjugated bilirubin by 42\%, suggesting UGT1A1 induction. Efavirenz also decreased conjugated bilirubin by 26\%, suggesting induction of bile efflux transporters. Ritonavir-boosted darunavir had no effect on bilirubin concentrations. These results indicate that efavirenz may reduce concentrations of drugs or endogenous substances metabolized by UGT1A1 or excreted by bile efflux transporters.
This article was published in Ann Acad Med Singapore and referenced in Journal of AIDS & Clinical Research

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

  • 5th International Conference on HIV/AIDS, STDs and STIs
    November 13-14, 2017 Las Vegas, Nevada, USA
Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords