Unexpected drug-drug interactions in human immunodeficiency virus (HIV) therapy: Induction of ugt1a1 and bile efflux transporters by efavirenz

Lawrence Su Lee, Paul Pham, Charles Williams Flexner

Research output: Contribution to journalArticle

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

Original languageEnglish (US)
Pages (from-to)559-562
Number of pages4
JournalAnnals of the Academy of Medicine Singapore
Volume41
Issue number12
StatePublished - Dec 2012

Fingerprint

efavirenz
Virus Activation
Drug Interactions
Bile
Ritonavir
HIV
Confidence Intervals
Pharmaceutical Preparations
Bilirubin
Therapeutics
Serum
Hepatitis
Healthy Volunteers

Keywords

  • Drug transporters
  • Drug-drug interactions
  • Efavirenz
  • HIV therapy
  • UGt1A1

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Unexpected drug-drug interactions in human immunodeficiency virus (HIV) therapy: Induction of ugt1a1 and bile efflux transporters by efavirenz",
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",
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T2 - Induction of ugt1a1 and bile efflux transporters by efavirenz

AU - Lee, Lawrence Su

AU - Pham, Paul

AU - Flexner, Charles Williams

PY - 2012/12

Y1 - 2012/12

N2 - 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

AB - 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

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