Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz

Paul Pham, Craig Hendrix, Patricia Barditch-Crovo, Teresa Parsons, Wasif Khan, Michelle Parish, Christine Radebaugh, Kathryn Anne Carson, Gary E. Pakes, Roula Qaqish, Charles Williams Flexner

Research output: Contribution to journalArticle

Abstract

Background: Amprenavir (APV), fosamprenavir (FPV), lopinavir (LPV), ritonavir (RTV) and efavirenz (EFV) are to varying degrees substrates, inducers and inhibitors of CYP3A4. Coadministration of these drugs might result in complex pharmacokinetic drug-drug interactions. Methods: Two prospective, open-label, non-randomized studies evaluated APV and LPV steady-state pharmacokinetics in HIV-infected patients on APV 750 mg twice daily + LPV/RTV 533/133 mg twice daily with EFV (n=7) or without EFV (n=12) + background nucleosides (Study 1) and after switching FPV 1,400 mg twice daily for APV (n=10) (Study 2). Results: In Study 1 EFV and non-EFV groups did not differ in APV minimum plasma concentration (Cmin; 1.10 versus 1.06 μg/ml, P=0.89), area under the concentration-time curve (AUC; 17.46 versus 24.34 μg•h/ml, P=0.22) or maximum concentration (Cmax; 2.61 versus 4.33 μg/ml, P=0.08); for LPV there was no difference in Cmin (median: 3.66 versus 6.18 μg/ml, P=0.20), AUC (81.84 versus 93.75 μg•h/ml, P=0.37) or Cmax (10.36 versus 10.93 μg/ml, P=0.61). In Study 2, after switching from APV to FPV, APV Cmin increased by 58% (0.83 versus 1.30 μg/ml, P=0.0001), AUC by 76% (19.41 versus 34.24 μg•h/ml, P=0.0001), and Cmax by 75% (3.50 versus 6.14, P=0.001). Compared with historical controls, LPV and RTV pharmacokinetics were not changed. All treatment regimens were well tolerated. Seven of eight completers (88%) maintained HIV-1 RNA min, AUC, and Cmax without changing LPV or RTV pharmacokinetics or overall tolerability.

Original languageEnglish (US)
Pages (from-to)963-969
Number of pages7
JournalAntiviral Therapy
Volume12
Issue number6
StatePublished - 2007

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efavirenz
Lopinavir
Ritonavir
Pharmacokinetics
Area Under Curve
fosamprenavir
amprenavir
Drug Interactions
Nucleosides
Pharmaceutical Preparations
HIV-1

ASJC Scopus subject areas

  • Pharmacology

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Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz. / Pham, Paul; Hendrix, Craig; Barditch-Crovo, Patricia; Parsons, Teresa; Khan, Wasif; Parish, Michelle; Radebaugh, Christine; Carson, Kathryn Anne; Pakes, Gary E.; Qaqish, Roula; Flexner, Charles Williams.

In: Antiviral Therapy, Vol. 12, No. 6, 2007, p. 963-969.

Research output: Contribution to journalArticle

Pham, Paul ; Hendrix, Craig ; Barditch-Crovo, Patricia ; Parsons, Teresa ; Khan, Wasif ; Parish, Michelle ; Radebaugh, Christine ; Carson, Kathryn Anne ; Pakes, Gary E. ; Qaqish, Roula ; Flexner, Charles Williams. / Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz. In: Antiviral Therapy. 2007 ; Vol. 12, No. 6. pp. 963-969.
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title = "Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz",
abstract = "Background: Amprenavir (APV), fosamprenavir (FPV), lopinavir (LPV), ritonavir (RTV) and efavirenz (EFV) are to varying degrees substrates, inducers and inhibitors of CYP3A4. Coadministration of these drugs might result in complex pharmacokinetic drug-drug interactions. Methods: Two prospective, open-label, non-randomized studies evaluated APV and LPV steady-state pharmacokinetics in HIV-infected patients on APV 750 mg twice daily + LPV/RTV 533/133 mg twice daily with EFV (n=7) or without EFV (n=12) + background nucleosides (Study 1) and after switching FPV 1,400 mg twice daily for APV (n=10) (Study 2). Results: In Study 1 EFV and non-EFV groups did not differ in APV minimum plasma concentration (Cmin; 1.10 versus 1.06 μg/ml, P=0.89), area under the concentration-time curve (AUC; 17.46 versus 24.34 μg•h/ml, P=0.22) or maximum concentration (Cmax; 2.61 versus 4.33 μg/ml, P=0.08); for LPV there was no difference in Cmin (median: 3.66 versus 6.18 μg/ml, P=0.20), AUC (81.84 versus 93.75 μg•h/ml, P=0.37) or Cmax (10.36 versus 10.93 μg/ml, P=0.61). In Study 2, after switching from APV to FPV, APV Cmin increased by 58{\%} (0.83 versus 1.30 μg/ml, P=0.0001), AUC by 76{\%} (19.41 versus 34.24 μg•h/ml, P=0.0001), and Cmax by 75{\%} (3.50 versus 6.14, P=0.001). Compared with historical controls, LPV and RTV pharmacokinetics were not changed. All treatment regimens were well tolerated. Seven of eight completers (88{\%}) maintained HIV-1 RNA min, AUC, and Cmax without changing LPV or RTV pharmacokinetics or overall tolerability.",
author = "Paul Pham and Craig Hendrix and Patricia Barditch-Crovo and Teresa Parsons and Wasif Khan and Michelle Parish and Christine Radebaugh and Carson, {Kathryn Anne} and Pakes, {Gary E.} and Roula Qaqish and Flexner, {Charles Williams}",
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TY - JOUR

T1 - Amprenavir and lopinavir pharmacokinetics following coadministration of amprenavir or fosamprenavir with lopinavir/ritonavir, with or without efavirenz

AU - Pham, Paul

AU - Hendrix, Craig

AU - Barditch-Crovo, Patricia

AU - Parsons, Teresa

AU - Khan, Wasif

AU - Parish, Michelle

AU - Radebaugh, Christine

AU - Carson, Kathryn Anne

AU - Pakes, Gary E.

AU - Qaqish, Roula

AU - Flexner, Charles Williams

PY - 2007

Y1 - 2007

N2 - Background: Amprenavir (APV), fosamprenavir (FPV), lopinavir (LPV), ritonavir (RTV) and efavirenz (EFV) are to varying degrees substrates, inducers and inhibitors of CYP3A4. Coadministration of these drugs might result in complex pharmacokinetic drug-drug interactions. Methods: Two prospective, open-label, non-randomized studies evaluated APV and LPV steady-state pharmacokinetics in HIV-infected patients on APV 750 mg twice daily + LPV/RTV 533/133 mg twice daily with EFV (n=7) or without EFV (n=12) + background nucleosides (Study 1) and after switching FPV 1,400 mg twice daily for APV (n=10) (Study 2). Results: In Study 1 EFV and non-EFV groups did not differ in APV minimum plasma concentration (Cmin; 1.10 versus 1.06 μg/ml, P=0.89), area under the concentration-time curve (AUC; 17.46 versus 24.34 μg•h/ml, P=0.22) or maximum concentration (Cmax; 2.61 versus 4.33 μg/ml, P=0.08); for LPV there was no difference in Cmin (median: 3.66 versus 6.18 μg/ml, P=0.20), AUC (81.84 versus 93.75 μg•h/ml, P=0.37) or Cmax (10.36 versus 10.93 μg/ml, P=0.61). In Study 2, after switching from APV to FPV, APV Cmin increased by 58% (0.83 versus 1.30 μg/ml, P=0.0001), AUC by 76% (19.41 versus 34.24 μg•h/ml, P=0.0001), and Cmax by 75% (3.50 versus 6.14, P=0.001). Compared with historical controls, LPV and RTV pharmacokinetics were not changed. All treatment regimens were well tolerated. Seven of eight completers (88%) maintained HIV-1 RNA min, AUC, and Cmax without changing LPV or RTV pharmacokinetics or overall tolerability.

AB - Background: Amprenavir (APV), fosamprenavir (FPV), lopinavir (LPV), ritonavir (RTV) and efavirenz (EFV) are to varying degrees substrates, inducers and inhibitors of CYP3A4. Coadministration of these drugs might result in complex pharmacokinetic drug-drug interactions. Methods: Two prospective, open-label, non-randomized studies evaluated APV and LPV steady-state pharmacokinetics in HIV-infected patients on APV 750 mg twice daily + LPV/RTV 533/133 mg twice daily with EFV (n=7) or without EFV (n=12) + background nucleosides (Study 1) and after switching FPV 1,400 mg twice daily for APV (n=10) (Study 2). Results: In Study 1 EFV and non-EFV groups did not differ in APV minimum plasma concentration (Cmin; 1.10 versus 1.06 μg/ml, P=0.89), area under the concentration-time curve (AUC; 17.46 versus 24.34 μg•h/ml, P=0.22) or maximum concentration (Cmax; 2.61 versus 4.33 μg/ml, P=0.08); for LPV there was no difference in Cmin (median: 3.66 versus 6.18 μg/ml, P=0.20), AUC (81.84 versus 93.75 μg•h/ml, P=0.37) or Cmax (10.36 versus 10.93 μg/ml, P=0.61). In Study 2, after switching from APV to FPV, APV Cmin increased by 58% (0.83 versus 1.30 μg/ml, P=0.0001), AUC by 76% (19.41 versus 34.24 μg•h/ml, P=0.0001), and Cmax by 75% (3.50 versus 6.14, P=0.001). Compared with historical controls, LPV and RTV pharmacokinetics were not changed. All treatment regimens were well tolerated. Seven of eight completers (88%) maintained HIV-1 RNA min, AUC, and Cmax without changing LPV or RTV pharmacokinetics or overall tolerability.

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