Clinical Pharmacokinetics

, Volume 48, Issue 4, pp 211–241 | Cite as

Drug Interactions with New and Investigational Antiretrovirals

  • Kevin C. Brown
  • Sunita Paul
  • Angela D. M. Kashuba
Review Article

Abstract

More than 20 individual and fixed-dose combinations of antiretrovirals are approved for the treatment of human immunodeficiency virus (HIV) infection. However, owing to the ongoing limitations of drug resistance and adverse effects, new treatment options are still required. A number of promising new agents in existing or new drug classes are in development or have recently been approved by the US FDA. Since these agents will be used in combination with other new and existing antiretrovirals, understanding the potential for drug interactions between these compounds is critical to their appropriate use. This article summarizes the drug interaction potential of new and investigational protease inhibitors (darunavir), non-nucleoside reverse transcriptase inhibitors (etravirine and rilpivirine), chemokine receptor antagonists (maraviroc, vicriviroc and INCB 9471), integrase inhibitors (raltegravir and elvitegravir) and maturation inhibitors (bevirimat).

Keywords

Atorvastatin Ritonavir Efavirenz Indinavir Saquinavir 

Notes

Acknowledgements

This work was supported by Boehringer Ingelheim Pharmaceuticals, Inc. Dr Kashuba has received honoraria from Boehringer Ingelheim Pharmaceuticals, Inc. and Tibotec Pharmaceuticals, and grants from Merck, Pfizer, Tibotec, Abbott and Gilead. The other authors have no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Prezista® (darunavir) tablet: US prescribing information. Raritan (NJ): Tibotec Therapeutics, 2008 Dec [online]. Available from URL: http://www.prezista.com/prezista/documents/us_package_insert.pdf [Accessed 2009 Mar 25]
  2. 2.
    De Meyer S, Azijn H, Surleraux D, et al. TMC114, a novel human immunodeficiency virus type 1 protease inhibitor active against protease inhibitor-resistant viruses, including a broad range of clinical isolates. Antimicrob Agents Chemother 2005 Jun; 49(6): 2314–21PubMedCrossRefGoogle Scholar
  3. 3.
    Dierynck I, De Wit M, Gustin E, et al. Binding kinetics of darunavir to human immunodeficiency virus type 1 protease explain the potent antiviral activity and high genetic barrier. J Virol 2007 Dec; 81(24): 13845–51PubMedCrossRefGoogle Scholar
  4. 4.
    Sekar V, Spinosa-Guzman S, Lefebvre E, et al. Clinical pharmacology of TMC114 — a potent HIV protease inhibitor [abstract no. TUPE0083]. XVI International AIDS Conference; 2006 Aug 13–18; Toronto (ON)Google Scholar
  5. 5.
    Sekar V, De Meyer S, Vangeneugden T, et al. Pharmacokinetic/pharmacodynamic analyses of TMC114 in the POWER 1 and POWER 2 trials in treatment-experienced HIV-infected patients. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)Google Scholar
  6. 6.
    Profit L, Eagling VA, Back DJ. Modulation of P-glycoprotein function in human lymphocytes and Caco-2 cell monolayers by HIV-1 protease inhibitors. AIDS 1999 Sep 10; 13(13): 1623–7PubMedCrossRefGoogle Scholar
  7. 7.
    Lee LS, Soon GH, Shen P, et al. Efavirenz increases MRP1 efflux transporter function while darunavir inhibits MRP1 expression in healthy volunteers [abstract no. 705]. 16th Conference on Retroviruses and Opportunistic Infections; 2009 Feb 8–11; Montreal (QC)Google Scholar
  8. 8.
    Molina JM, Hill A. Darunavir (TMC114): a new HIV-1 protease inhibitor. Expert Opin Pharmacother 2007 Aug; 8(12): 1951–64PubMedCrossRefGoogle Scholar
  9. 9.
    Rittweger M, Arastéh K. Clinical pharmacokinetics of darunavir. Clin Pharmacokinet 2007; 46(9): 739–56PubMedCrossRefGoogle Scholar
  10. 10.
    TMC114 investigator’s brochure. 7th ed. Co Cork, Ireland: Tibotec, 2006Google Scholar
  11. 11.
    Sekar, V, Guzman S, Stevens T, et al. Absolute bioavailability of TMC114 administered in the absence and presence of low-dose ritonavir [abstract no. 86]. 7th International Workshop on Clinical Pharmacology of HIV Therapy; 2006 Apr 20–22; LisbonGoogle Scholar
  12. 12.
    Sekar V, Kestens D, Spinosa-Guzman S, et al. The effect of different meal types on the pharmacokinetics of darunavir (TMC114)/ritonavir in HIV-negative healthy volunteers. J Clin Pharmacol 2007 Apr; 47(4): 479–84PubMedCrossRefGoogle Scholar
  13. 13.
    Busse KH, Penzak SR. Darunavir: a second-generation protease inhibitor. Am J Health Syst Pharm 2007 Aug 1; 64(15): 1593–602PubMedCrossRefGoogle Scholar
  14. 14.
    Sekar VJ, Lefebvre E, Mariën K, et al. Pharmacokinetic interaction between the HIV protease inhibitors TMC114 and saquinavir, in the presence of low-dose ritonavir [abstract no. 959]. 44th Annual Meeting of the Infectious Disease Society of America; 2006 Oct 12–15; Toronto (ON)Google Scholar
  15. 15.
    Sekar VJ, Lefebvre E, Boogaerts G, et al. Pharmacokinetic interaction between the protease inhibitors TMC114 and lopinavir/ritonavir [abstract no. A-367]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  16. 16.
    Prezista® (darunavir): summary of product characteristics. London: Janssen-Cilag International NV, 2007Google Scholar
  17. 17.
    Sekar VJ, Spinosa-Guzman S, De Paepe E, et al. Darunavir/ritonavir pharmacokinetics following coadministration with clarithromycin in healthy volunteers. J Clin Pharmacol 2008 Jan; 48(1): 60–5PubMedCrossRefGoogle Scholar
  18. 18.
    Sekar VJ, Lefebvre E, De Paepe E, et al. Pharmacokinetic interaction between darunavir boosted with ritonavir and omeprazole or ranitidine in human immunodeficiency virus-negative healthy volunteers. Antimicrob Agents Chemother 2007 Mar; 51(3): 958–61PubMedCrossRefGoogle Scholar
  19. 19.
    Abel S, Ridgway C, Hamlin J, et al. An open, randomized, 2-way crossover study to investigate the effects of darunavir/ritonavir on the pharmacokinetics of maraviroc in healthy subjects [abstract no. 55]. 8th International Workshop on Pharmacology of HIV Therapy; 2007 Apr 16–18; BudapestGoogle Scholar
  20. 20.
    Pecini R, Vangeneugden T, Falcon R, et al. Darunavir in combination with other medications: pharmacokinetic interactions [poster no. S3-5]. Presented at the American Conference for the Treatment of HIV (ACTHIV) 2007; 2007 May 31–Jun 3; Dallas (TX)Google Scholar
  21. 21.
    Sekar V, De Paepe E, Vangeneugden T, et al. Absence of an interaction between the potent HIV protease inhibitor TMC114 and the fusion inhibitor enfuvirtide in the POWER 3 analysis [abstract no. 54]. 7th International Workshop on Clinical Pharmacology of HIV Therapy; 2006 Apr 20–22; LisbonGoogle Scholar
  22. 22.
    Sekar VJ, Lefebvre E, Mariën K, et al. Pharmacokinetic interaction between the antiretroviral agents TMC114 and nevirapine, in the presence of low-dose ritonavir [abstract no. 956]. 44th Annual Meeting of the Infectious Disease Society of America; 2006 Oct 12–15; Toronto (ON)Google Scholar
  23. 23.
    Hoetelmans RM, Mariën K, De Pauw M, et al. Pharmacokinetic interaction between TMC114/ritonavir and tenofovir disoproxil fumarate in healthy volunteers. Br J Clin Pharmacol 2007 Nov; 64(5): 655–61PubMedCrossRefGoogle Scholar
  24. 24.
    Boffito M, Winston A, Jackson A, et al. Pharmacokinetics and antiretroviral response to darunavir/ritonavir and etravirine combination in patients with high-level viral resistance. AIDS 2007 Jul 11; 21(11): 1449–55PubMedCrossRefGoogle Scholar
  25. 25.
    Intelence™ (etravirine) tablets: US prescribing information. Raritan (NJ): Tibotec Therapeutics, 2008 Jan [online]. Available from URL: http://www.intelence-info.com/intelence/assets/pdf/INTELENCE_PI.pdf [Accessed 2009 Feb 19]
  26. 26.
    Schöller-Gyüre M, Kakuda TN, Sekar V, et al. Pharmacokinetics of darunavir/ritonavir and TMC125 alone and coadministered in HIV-negative volunteers. Antivir Ther 2007; 12(5): 789–96PubMedGoogle Scholar
  27. 27.
    Sekar VJ, De Pauw M, Mariën K, et al. Pharmacokinetic interaction between TMC114/r and efavirenz in healthy volunteers. Antivir Ther 2007; 12(4): 509–14PubMedGoogle Scholar
  28. 28.
    Lipitor® (atorvastatin calcium) tablets: US prescribing information. New York: Pfizer Inc, 2009 Feb [online]. Available from URL: http://www.pfizer.com/files/products/uspi_lipitor.pdf [Accessed 2009 Mar 27]
  29. 29.
    Chuck SK, Penzak SR. Risk-benefit of HMG-CoA reductase inhibitors in the treatment of HIV protease inhibitor-related hyperlipidaemia. Expert Opin Drug Saf 2002 May; 1(1): 5–17PubMedCrossRefGoogle Scholar
  30. 30.
    Sekar VJ, Spinosa-Guzman S, Mariën K, et al. Pharmacokinetic drug-drug interaction between the new HIV protease inhibitor darunavir (TMC114) and the lipid-lowering agent pravastatin [abstract no. 55]. 8th International Workshop on Pharmacology of HIV Therapy; 2007 Apr 16–18; BudapestGoogle Scholar
  31. 31.
    Sekar VJ, Lefebvre E, Felicione E, et al. Pharmacokinetic interaction between ethinyl estradiol, norethindrone and TMC114, a new protease inhibitor [abstract no. A-368]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  32. 32.
    HIV Insite. Antiretroviral management charts and tables [online]. Available from URL: http://www.hivinsite.com/InSite?page=ar-00-00-02 [Accessed 2009 Feb 19]
  33. 33.
    Sekar V, De Paepe E, De Marez T, et al. Pharmacokinetic interaction between TMC114, a new protease inhibitor, and the selective serotonin reuptake inhibitors, paroxetine and sertraline [abstract no. P295]. 8th International Congress on Drug Therapy for HIV; 2006 Nov 12–16; GlasgowGoogle Scholar
  34. 34.
    Carbon C, Poole MD. The role of newer macrolides in the treatment of community-acquired respiratory tract infection: a review of experimental and clinical data. J Chemother 1999 Apr; 11(2): 107–18PubMedGoogle Scholar
  35. 35.
    Rodvold K. Clinical pharmacokinetics of clarithromycin. Clin Pharmacokinet 1999 Nov; 37(5): 385–98PubMedCrossRefGoogle Scholar
  36. 36.
    Ouellet D, Hsu A, Granneman GR, et al. Pharmacokinetic interaction between ritonavir and clarithromycin. Clin Pharmacol Ther 1998 Oct; 64(4): 355–62PubMedCrossRefGoogle Scholar
  37. 37.
    Brophy DF, Israel DS, Pastor A, et al. Pharmacokinetic interaction between amprenavir and clarithromycin in healthy male volunteers. Antimicrob Agents Chemother 2000 Apr; 44(4): 978–84PubMedCrossRefGoogle Scholar
  38. 38.
    Boruchoff SE, Sturgill MG, Grasing KW, et al. The steady-state disposition of indinavir is not altered by the concomitant administration of clarithromycin. Clin Pharmacol Ther 2000 Apr; 67(4): 351–9PubMedCrossRefGoogle Scholar
  39. 39.
    Sekar VJ, Lefebvre E, De Pauw M, et al. Pharmacokinetic interaction between TMC114 and ketoconazole, in the absence and presence of low-dose ritonavir [abstract no. 960]. 44th Annual Meeting of the Infectious Disease Society of America; 2006 Oct 12–15; Toronto (ON)Google Scholar
  40. 40.
    Nadler JP, Berger DS, Blick G, et al., for the TMC125-C223 Writing Group. Efficacy and safety of etravirine (TMC125) in patients with highly resistant HIV-1: primary 24-week analysis. AIDS 2007 Mar 30;21 (6): F1–10Google Scholar
  41. 41.
    PubChem. Etravirine—compound summary (CID 193962) [online]. Available from URL: http://pubchem.ncbi.nlm.nih.gov.libproxy.lib.unc.edu/summary/summary.cgi?cid=193962&loc=ec_rcs [Accessed 2009 Feb 19]
  42. 42.
    Vingerhoets J, Azijn H, Fransen E, et al. TMC125 displays a high genetic barrier to the development of resistance: evidence from in vitro selection experiments. J Virol 2005 Oct; 79(20): 12773–82PubMedCrossRefGoogle Scholar
  43. 43.
    Andries K, Azijn H, Thielemans T, et al. TMC125, a novel next-generation nonnucleoside reverse transcriptase inhibitor active against nonnucleoside reverse transcriptase inhibitor-resistant human immunodeficiency virus type 1. Antimicrob Agents Chemother 2004 Dec; 48(12): 4680–6PubMedCrossRefGoogle Scholar
  44. 44.
    Ramanathan S, West S, Kakuda TN, et al. Lack of clinically relevant drug interactions between ritonavir-boosted elvitegravir and TMC125 [abstract no. H-1049]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  45. 45.
    Kakuda TN, Schöller-Gyüre M, Woodfall B, et al. TMC125 in combination with other medications: summary of drug-drug interaction studies [abstract no. PL5.2]. 8th International Congress on Drug Therapy for HIV; 2006 Nov 12–16; GlasgowGoogle Scholar
  46. 46.
    Kakuda TN, Kiser JJ. 7th International Workshop on Clinical Pharmacology of HIV Therapy, 20–22 April 2006, Lisbon, Portugal. Expert Opin Pharmacother 2006 Aug; 7(11): 1519–33PubMedCrossRefGoogle Scholar
  47. 47.
    Israel D, Kakuda TN, Schöller-Gyüre M, et al. TMC125 in combination with medications commonly used in HIV infection: summary of drug-drug interactions [poster no. S3-8]. American Conference for the Treatment of HIV (ACTHIV) 2007; 2007 May 31–Jun 3; Dallas (TX)Google Scholar
  48. 48.
    Schöller-Gyüre M, Kakuda TN, De Smedt G, et al. Pharmacokinetics (PK) of TMC125 in QD and BID regimens in HIV-1 negative volunteers [abstract no. A-1427]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  49. 49.
    Schöller-Gyüre M, Leemans R, Beets G, et al. Effect of food on the oral bioavailability of the phase III formulation of TMC125 [abstract no. 80]. 7th International Workshop on Clinical Pharmacology of HIV Therapy; 2006 Apr 20–22; LisbonGoogle Scholar
  50. 50.
    Schöller-Gyüre M, Kakuda TN, De Smedt G, et al. Pharmacokinetics of TMC125 in HIV-negative volunteers with mild and moderate hepatic impairment [abstract no. A-1428]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  51. 51.
    Etravirine: R165335, TMC 125, TMC-125, TMC125. Drugs R & D 2006; 7 (6): 367-73Google Scholar
  52. 52.
    Hsu A, Granneman GR, Bertz RJ. Ritonavir: clinical pharmacokinetics and interactions with other anti-HIV agents. Clin Pharmacokinet 1998 Oct; 35(4): 275–91PubMedCrossRefGoogle Scholar
  53. 53.
    Baede P, Piscitelli S, Graham N, et al. Drug interactions with TMC125, a potent next generation NNRTI [abstract no. A-1827]. 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy; 2002 Sep 27–30; San Diego (CA)Google Scholar
  54. 54.
    van der Lee MJ, Blenke AA, Rongen GA, et al. Interaction study of the combined use of paroxetine and fosamprenavir-ritonavir in healthy subjects. Antimicrob Agents Chemother 2007 Nov; 51(11): 4098–104PubMedCrossRefGoogle Scholar
  55. 55.
    Schöller-Gyüre M, Woodfall B, Bollen S, et al. Pharmacokinetics (PK) of amprenavir (APV) and TMC125 in HIV infected volunteers receiving TMC125 with fosamprenavir/ritonavir (fosAPV/RTV) [abstract no. A-370]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  56. 56.
    McCallister S, Sabo J, Galitz L, et al. An open-label steady state investigation of the pharmacokinetics (PK) of tipranavir (TPV) and ritonavir (RTV) and their effects on cytochrome P-450 (3A4) activity in normal healthy volunteers (BI 1182.5) [abstract no. 434]. 9th Conference on Retroviruses and Opportunistic Infections; 2002 Feb 24–28; Seattle (WA)Google Scholar
  57. 57.
    Vourvahis M, Dumond J, Patterson K, et al. Effects of tipranavir/ritonavir on the activity of hepatic and intestinal cytochrome P450 3A4/5 and P-glycoprotein: implications for drug interactions [abstract no. 563]. 14th Conference on Retroviruses and Opportunistic Infections; 2007 Feb 25–28; Los Angeles (CA)Google Scholar
  58. 58.
    Schöller M, Kraft M, Hoetelmans R, et al. Significant decrease in TMC125 exposures when co-administered with tipranavir boosted with ritonavir in healthy subjects [abstract no. 583]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)Google Scholar
  59. 59.
    Harris M, Zala C, Ramirez S, et al. Pharmacokinetics and safety of adding TMC125 to stable regimens of saquinavir, lopinavir, ritonavir, and NRTI in HIV+ adults [abstract no. 575b]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)Google Scholar
  60. 60.
    Schöller M, Hoetelmans R, Bollen S, et al. No significant interaction between TMC125 and didanosine (ddI) in healthy volunteers [abstract no. WePe3.3C16]. 3rd IAS Conference on HIV Pathogenesis and Treatment; 2005 Jul 24–27; Rio de JaneiroGoogle Scholar
  61. 61.
    Schöller M, Hoetelmans R, Bollen S, et al. No significant interaction between TMC125 and didanosine (ddI) in healthy volunteers [abstract no. 29]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  62. 62.
    Boffito M, Jackson A, Lamorde M, et al. Evaluation of the pharmacokinetics and safety of etravirine administered once and twice daily following two weeks of treatment with efavirenz in healthy volunteers [abstract no. H-4057]. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2008 Oct 25–28; Washington, DCGoogle Scholar
  63. 63.
    Anderson MS, Kakuda TN, Miller JL, et al. Pharmacokinetic evaluation of non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC125 and integrase inhibitor (InSTI) raltegravir (RAL) in healthy subjects [abstract no. TUPDB02]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; SydneyGoogle Scholar
  64. 64.
    Schöller-Gyüre M, Kakuda TN, Bollen S, et al. No pharmacokinetic interaction between TMC125 (etravirine; ETR) and paroxetine in HIV-negative volunteers [abstract no. P4.3/01]. 11th European AIDS Conference; 2007 Oct 24–27; MadridGoogle Scholar
  65. 65.
    Schöller-Gyüre M, De Smedt G, Vanaken H, et al. TMC125 bioavailability is not affected by ranitidine and omeprazole [abstract no. TUPE0082]. XVI International AIDS Conference; 2006 Aug 13–18; Toronto (ON)Google Scholar
  66. 66.
    Eap CB, Cuendet C, Baumann P. Binding of d-methadone, l-methadone, and dl-methadone to proteins in plasma of healthy volunteers: role of the variants of α1-acid glycoprotein. Clin Pharmacol Ther 1990 Mar; 47(3): 338–46PubMedCrossRefGoogle Scholar
  67. 67.
    Kharasch ED, Hoffer C, Whittington D, et al. Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone. Clin Pharmacol Ther 2004 Sep; 76(3): 250–69PubMedCrossRefGoogle Scholar
  68. 68.
    Schöller-Gyüre M, van den Brink W, Kakuda T, et al. Pharmacokinetic and pharmacodynamic study of the concomitant administration of methadone and TMC125 in HIV-negative volunteers. J Clin Pharmacol 2008; 48: 322–9PubMedCrossRefGoogle Scholar
  69. 69.
    Intelence® (etravirine) tablets: US prescribing information. Raritan (NJ): Tibotec Therapeutics, 2008 Jan [online]. Available from URL: http://www.intelence-info.com/intelence/assets/pdf/INTELENCE_PI.pdf [Accessed 2009 Apr 1]
  70. 70.
    Schöller-Gyüre M, Debroye C, Woodfall B, et al. Pharmacokinetic interaction between TMC125 and clarithromycin [abstract no. 962]. 44th Annual Meeting of the Infectious Disease Society of America; 2006 Oct 12–15; Toronto (ON)Google Scholar
  71. 71.
    Schöller-Gyüre M, Woodfall B, Debroye C, et al. Pharmacokinetic interaction between TMC125 and rifabutin [abstract no. 963]. 44th Annual Meeting of the Infectious Disease Society of America; 2006 Oct 12–15; Toronto (ON)Google Scholar
  72. 72.
    Schöller-Gyüre M, Kakuda TN, De Smedt G, et al. Pharmacokinetic interaction between the non-nucleoside reverse transcriptase inhibitors (NNRTI) TMC 125 and atorvastatin in HIV-negative volunteers [abstract no. WEPEA 106]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; SydneyGoogle Scholar
  73. 73.
    PubChem. Rilpivirine — compound summary (CID 6451164) [online]. Available from URL: http://pubchem.ncbi.nlm.nih.gov.libproxy.lib.unc.edu/summary/summary.cgi?cid=6451164&loc=ec_rcs [Accessed 2009 Feb 19]
  74. 74.
    Janssen PA, Lewi PJ, Arnold E, et al. In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cya-noethenyl]-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile (R278474, rilpivirine). J Med Chem 2005 Mar 24; 48(6): 1901–9PubMedCrossRefGoogle Scholar
  75. 75.
    Goebel F, Yakovlev A, Pozniak AL, et al. Short-term antiviral activity of TMC278 — a novel NNRTI — in treatment-naïve HIV-1-infected subjects. AIDS 2006 Aug 22; 20(13): 1721–6PubMedCrossRefGoogle Scholar
  76. 76.
    Hoetelmans R, Kestens D, Mariën K, et al. Effect of food and multiple-dose pharmacokinetics of TMC278 as an oral tablet formulation: healthy volunteers [abstract no. TuPe3.1B10]. 3rd IAS Conference on HIV Pathogenesis and Treatment; 2005 Jul 24–27; Rio de JaneiroGoogle Scholar
  77. 77.
    Van Heeswijk R, Hoetelmans RMW, Kestens D, et al. The pharmacokinetic (PK) interaction between TMC278, a next generation non-nucleoside reverse transcriptase inhibitor (NNRTI), and once daily darunavir/ritonavir (DRV/r) in HIV-negative volunteers [abstract no. H-1042]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  78. 78.
    Hoetelmans R, Kestens D, Stevens M, et al. Pharmacokinetic interaction between the novel non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 and tenofovir disoproxil fumarate (TDF) in healthy volunteers [abstract no. 18]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  79. 79.
    Van Heeswijk RPG, Hoetelmans RMW, Aharchi F, et al. The pharmacokinetic (PK) interaction between atorvastatin (AVS) and TMC278, a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), in HIV-negative volunteers [abstract no. P4.3/04]. 11th European AIDS Conference; 2007 Oct 24–27; MadridGoogle Scholar
  80. 80.
    Van Heeswijk RP, Hoetelmans RM, Kestens D, et al. The pharmacokinetic interaction between ketoconazole and TMC278, an investigational non-nucleoside reverse transcriptase inhibitor in healthy, HIV-negative subjects [abstract no. TUPE0087]. 16th International AIDS Conference; 2006 August 13–18; Toronto (ON)Google Scholar
  81. 81.
    Schöller-Gyüre M, Debroye C, Vyncke V, et al. The effects of CYP3A4 modulation on the pharmacokinetics of TMC278, an investigational, non-nucleoside reverse transcriptase inhibitor (NNRTI) [abstract no. 45]. 7th International Workshop on Clinical Pharmacology of HIV Therapy; 2006 Apr 20–22; LisbonGoogle Scholar
  82. 82.
    Van Heeswijk R, Hoetelmans R, Kestens D, et al. The pharmacokinetic (PK) interaction between famotidine and TMC278, a next generation non-nucleoside reverse transcriptase inhibitor (NNRTI), in HIV-negative volunteers [abstract no. TUPDB01]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 July 22–25; SydneyGoogle Scholar
  83. 83.
    PubChem. Maraviroc — compound summary (CID 3002977) [online]. Available from URL: http://pubchem.ncbi.nlm.nih.gov.libproxy.lib.unc.edu/summary/summary.cgi?cid=3002977&loc=ec_rcs [Accessed 2009 Feb 19]
  84. 84.
    Dorr P, Westby M, Dobbs S, et al. Maraviroc (UK-427,857), a potent, orally bioavailable, and selective small-molecule inhibitor of chemokine receptor CCR5 with broad-spectrum anti-human immunodeficiency virus type 1 activity. Antimicrob Agents Chemother 2005 Nov; 49(11): 4721–32PubMedCrossRefGoogle Scholar
  85. 85.
    Hyland R, Jones B, Muirhead G. In vitro assessment of the CYP-based drug-drug interaction potential of UK-427,857 [poster no. 5.9]. 5th International Workshop on the Clinical Pharmacology of HIV Therapy; 2004 Mar 11–13; RomeGoogle Scholar
  86. 86.
    Abel S, Russell D, Ridgway C, et al. The effect of CCR5 antagonist UK-427,857, on the pharmacokinetics of CYP3A4 substrates in healthy volunteers [poster no. 5.7]. 5th International Workshop on the Clinical Pharmacology of HIV Therapy; 2004 Mar 11–13; RomeGoogle Scholar
  87. 87.
    Abel S, Russell D, Whitlock LA, et al. Effect of maraviroc on the pharmacokinetics of midazolam, lamivudine/zidovudine, and ethinyloestradiol/levonorgestrel in healthy volunteers. Br J Clin Pharmacol 2008 Apr; 65 Suppl. 1: 19–26PubMedCrossRefGoogle Scholar
  88. 88.
    Walker DK, Abel S, Comby P, et al. Species differences in the disposition of the CCR5 antagonist, UK-427,857, a new potential treatment for HIV. Drug Metab Dispos 2005 Apr; 33(4): 587–95PubMedCrossRefGoogle Scholar
  89. 89.
    Pfizer Inc. Maraviroc tablets NDA 22-128: Antiviral Drugs Advisory Committee briefing document, April 24,2007 [online]. Available from URL: http://www.fda.gov/OHRMS/DOCKETS/AC/07/briefing/2007-4283b1-01-Pfizer.pdf [Accessed 2009 Feb 19]
  90. 90.
    Selzentry® (maraviroc) tablets: US prescribing information. New York: Pfizer Labs, 2008 Nov [online]. Available from URL: http://media.pfizer.com/files/products/uspi_maraviroc.pdf [Accessed 2009 Mar 27]
  91. 91.
    Abel S, Russell D, Whitlock LA, et al. Assessment of the absorption, metabolism and absolute bioavailability of maraviroc in healthy male subjects. Br J Clin Pharmacol 2008 Apr; 65 Suppl. 1: 60–7PubMedCrossRefGoogle Scholar
  92. 92.
    Abel S, Van der Ryst E, Muirhead GJ, et al. Pharmacokinetics of single and multiple oral doses of UK-427,857 — a novel CCR5 antagonist in healthy volunteers [abstract no. 547]. 10th Conference on Retroviruses and Opportunistic Infections; 2003 Feb 10–14; Boston (MA)Google Scholar
  93. 93.
    Abel S, van der Ryst E, Rosario MC, et al. Assessment of the pharmacokinetics, safety and tolerability of maraviroc, a novel CCR5 antagonist, in healthy volunteers. Br J Clin Pharmacol 2008 Apr; 65 Suppl. 1: 5–18PubMedCrossRefGoogle Scholar
  94. 94.
    Russell D, Ridgway C, Taylor-Worth R, et al. Pharmacokinetics special populations and toxicity comparison of the pharmacokinetics of maraviroc (UK-427,857) in healthy Asian and Caucasian subjects [abstract no. 41]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  95. 95.
    Abel S, Ridgway C, Hamlin J, et al. An open, parallel group study to compare the pharmacokinetics, safety and toleration of a single oral dose of mar-aviroc in subjects with mild and moderate hepatic impairment with subjects with normal hepatic function [abstract no. 8]. 8th International Workshop on Pharmacology of HIV Therapy; 2007 Apr 16–18; BudapestGoogle Scholar
  96. 96.
    Muirhead G, Pozniak A, Gazzard B, et al. A novel probe drug interaction study to investigate the effect of selected ARV combinations on the pharmacokinetics of a single oral dose of UK-427,857 in HIV +ve subjects [abstract no. 663]. 12th Conference on Retroviruses and Opportunistic Infections; 2005 Apr 22–25; Boston (MA)Google Scholar
  97. 97.
    Pozniak AL, Boffito M, Russell D, et al. A novel probe drug interaction study to investigate the effect of selected antiretroviral combinations on the pharmacokinetics of a single oral dose of maraviroc in HIV-positive subjects. Br J Clin Pharmacol 2008 Apr; 65 Suppl. 1: 54–9PubMedCrossRefGoogle Scholar
  98. 98.
    Abel S, Russell C, Ridgway C, et al. The effect of CYP3A4 inhibitors on the pharmacokinetics of CCR5 antagonist UK-427,857, in healthy volunteers [poster no. 5.8]. 5th International Workshop on the Clinical Pharmacology of HIV Therapy; 2004 Mar 11–13; RomeGoogle Scholar
  99. 99.
    Abel S, Russell D, Taylor-Worth RJ, et al. Effects of CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol 2008 Apr; 65 Suppl. 1: 27–37PubMedCrossRefGoogle Scholar
  100. 100.
    Muirhead G, Ridgway C, Leahy D, et al. A study to investigate the combined coadministration of P450 CYP3A4 inhibitors and inducers on the pharmacokinetics of the novel CCR5 inhibitor UK-427,857 [abstract no. P284]. 7th International Congress on Drug Therapy for HIV; 2004 Nov 14–18; GlasgowGoogle Scholar
  101. 101.
    Abel S, Jenkins TM, Whitlock LA, et al. Effects of CYP3A4 inducers with and without CYP3A4 inhibitors on the pharmacokinetics of maraviroc in healthy volunteers. Br J Clin Pharmacol 2008 Apr; 65 Suppl. 1: 38–46PubMedCrossRefGoogle Scholar
  102. 102.
    Abel S, Taylor-Worth R, Ridgway C, et al. Effect of boosted tipranavir on the pharmacokinetics of maraviroc (UK 427,857) in healthy volunteers [abstract no. LBPE4.3/15]. 10th European AIDS Conference; 2005 Nov 17–20; DublinGoogle Scholar
  103. 103.
    Muirhead G, Abel S, Russell D, et al. An investigation of the effects of atazanavir and ritonavir boosted atazanavir on the pharmacokinetics of the novel CCR5 inhibitor UK-427,857 [abstract no. P283]. 7th International Congress on Drug Therapy for HIV; 2004 Nov 14–18; GlasgowGoogle Scholar
  104. 104.
    Russell D, Abel S, Hackman F, et al. The effect of maraviroc (UK-427,857) on the pharmacokinetics of 3TC/AZT (Combivir™) in healthy subjects [abstract no. 30]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  105. 105.
    Jenkins T, Abel S, Russell D, et al. The effect of P450 inducers on the pharmacokinetics of CCR5 antagonist UK-427,857, in healthy volunteers [poster no. 5.4]. 5th International Workshop on the Clinical Pharmacology of HIV Therapy; 2004 Mar 11–13; RomeGoogle Scholar
  106. 106.
    Davis J, Schöller-Gyüre M, Kakuda TN, et al. An open, randomized, two-period, crossover study in 2 cohorts to investigate the effect of steady-state TMC125 and the combination of TMC125/darunavir/ritonavir on the steady-state pharmacokinetics of oral maraviroc in healthy subjects [abstract no. P4.3/02]. 11th European AIDS Conference/EACS; 2007 Oct 24–27; MadridGoogle Scholar
  107. 107.
    Ramanathan S, West S, Abel S, et al. Pharmacokinetics of coadministered ritonavir-boosted elvitegravir plus maraviroc [abstract no. H-1050]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  108. 108.
    Andrews E, Glue P, Labadie R, et al. A pharmacokinetic (PK) study to evaluate an interaction between maraviroc (MVC) and raltegravir (RAL) in healthy adults [abstract no. H-4055]. 48th Interscience Conference on Antimicrobial Agents and Chemotherapy/IDSA 46th Annual Meeting; 2008 Oct 25–28; Washingtion, DCGoogle Scholar
  109. 109.
    Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [online]. Available from URL: http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf [Accessed 2009 Mar 27]
  110. 110.
    Strizki JM, Tremblay C, Xu S, et al. Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1. Antimicrob Agents Chemother 2005 Dec; 49(12): 4911–9PubMedCrossRefGoogle Scholar
  111. 111.
    Ghosal A, Ramanathan R, Yuan Y, et al. Identification of human liver cytochrome P450 enzymes involved in biotransformation of vicriviroc, a CCR5 receptor antagonist. Drug Metab Dispos 2007 Dec; 35(12): 2186–95PubMedCrossRefGoogle Scholar
  112. 112.
    Li C, Keung A, Morrison RA, et al. Vicriviroc, a novel CCR5 inhibitor, is not a P-glycoprotein substrate in vitro. Retrovirology 2005; 2 Suppl. 1: P1–58Google Scholar
  113. 113.
    Schürmann D, Fätkenheuer G, Reynes J, et al. Antiviral activity, pharmacokinetics and safety of vicriviroc, an oral CCR5 antagonist, during 14-day monotherapy in HIV-infected adults. AIDS 2007 Jun 19; 21(10): 1293–9PubMedCrossRefGoogle Scholar
  114. 114.
    Keung A, Sansone A, Caceres M, et al. Effect of food on bioavailability of SCH 417690 in healthy volunteers [abstract no. A-1200]. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2005 Dec 16–19; Washington, DCGoogle Scholar
  115. 115.
    Sansone A, Seiberling M, Kraan M, et al. Similar increase in SCH 417690 plasma exposure with coadministration of varying doses of ritonavir in healthy volunteers [abstract no. 78]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  116. 116.
    Sansone A, Keung A, Tetteh E, et al. Pharmacokinetics of vicriviroc are not affected in combination with five different protease inhibitors boosted by ritonavir [abstract no. 582]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)Google Scholar
  117. 117.
    Sansone A, Saltzman M, Rosenberg M, et al. Pharmacokinetics of new drugs pharmacokinetics of SCH 417690 administered alone or in combination with ritonavir or lopinavir/ritonavir [abstract no. 83]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  118. 118.
    Sansone-Parsons A, Keung A, Caceres M, et al. The addition of tipranavir has no impact on the pharmacokinetics of vicriviroc when coadministered with a potent CYP3A4 inhibitor such as ritonavir [abstract no. 57]. 8th International Workshop on Pharmacology of HIV Therapy; 2007 Apr 16–18; BudapestGoogle Scholar
  119. 119.
    Sansone A, Guillaume M, Kraan M, et al. The pharmacokinetics of SCH 417690 when administered alone and in combination with lamivudine/zidovudine [abstract no. 84]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  120. 120.
    Sansone A, Guillaume M, Kraan M, et al. Pharmacokinetics of SCH 417690 administered alone or in combination with tenofovir [abstract no. 85]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  121. 121.
    Sansone A, Saltzman M, Rosenberg M, et al. Pharmacokinetics of SCH 417690 administered alone or in combination with ritonavir and efavirenz in healthy volunteers [abstract no. 79]. 6th International Workshop on Clinical Pharmacology of HIV Therapy; 2005 Apr 28–30; Quebec City (QC)Google Scholar
  122. 122.
    Shin N, Solomon K, Wang KH, et al. INCB 9471 is a non-competitive small molecule antagonist of CCR5 [abstract no. H-1032]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  123. 123.
    Cohen C, DeJesus E, Mills A, et al. Potent antiretroviral activity of the once-daily CCR5 antagonist INCB009471 over 14 days of monotherapy [abstract no. TUAB106]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 July 22–25; SydneyGoogle Scholar
  124. 124.
    Troy S, Emm T, Yeleswaram S, et al. Single and multiple dose pharmacokinetics of INCB009471: a potent antagonist of CCR5 co-receptor [abstract no. H-1034]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  125. 125.
    Troy S, Emm T, Yeleswaram S, et al. Effect of ritonavir on the pharmacokinetics of INCB009471: a potent antagonist of the CCR5 co-receptor [abstract no. H-1035]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  126. 126.
    Isentress™ (raltegravir) tablets: US prescribing information. Whitehouse Station (NJ); Merck & Co., Inc., 2009 Jan [online]. Available from URL: http://www.merck.com/product/usa/pi_circulars/i/isentress/isentress_pi.pdf [Accessed 2009 Mar 27]
  127. 127.
    Roquebert B, Damond F, Collin G, et al.; The French ANRS HIV-2 Cohort (ANRS CO 05 VIH-2). Polymorphism of HIV-2 integrase gene and in vitro phenotypic susceptibility of HIV-2 clinical isolates to integrase inhibitors: raltegravir and elvitegravir [abstract no. 83]. Antivir Ther 2007; 12: S92Google Scholar
  128. 128.
    Kassahun K, McIntosh I, Cui D, et al. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos 2007 Sep; 9(35): 1657–63CrossRefGoogle Scholar
  129. 129.
    Petry AS, Wenning LA, Laethem M, et al. Safety, tolerability, and pharmacokinetics after single and multiple doses of MK-0518 in healthy subjects [abstract no. A-376]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  130. 130.
    Markowitz M, Morales-Ramirez JO, Nguyen BY, et al. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naïve HIV-1-infected individuals. J Acquir Immune Defic Syndr 2006 Dec 15; 43(5): 509–15PubMedCrossRefGoogle Scholar
  131. 131.
    Wenning L, Anderson M, Petry A, et al. Raltegravir (RAL) dose proportionality and effect of food [abstract no. H-1046]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar
  132. 132.
    Iwamoto M, Hanley W, Petry A, et al. Lack of a clinically important effect of moderate hepatic insufficiency and severe renal insufficiency on raltegravir pharmacokinetics. Antimicrob Agents Chemother. Epub 2009 Feb 17Google Scholar
  133. 133.
    Vourvahis M, Kashuba AD. Mechanisms of pharmacokinetic and pharmacodynamic drug interactions associated with ritonavir-enhanced tipranavir. Pharmacotherapy 2007 Jun; 27(6): 888–909PubMedCrossRefGoogle Scholar
  134. 134.
    Iwamoto M, Wenning LA, Petry AS, et al. Minimal effect of ritonavir (RTV) and efavirenz (EFV) on the pharmacokinetics (PK) of Mk-0518 [abstract no. A-373]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  135. 135.
    Wenning LA, Hanley H, Stone J, et al. Effect of tipranavir + ritonavir TPV + RTV on pharmacokinetics of MK-0518 [abstract no. A-374]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  136. 136.
    Merck Research Laboratories. FDA Antiviral Drugs Advisory Committee Meeting: Isentress™ (raltegravir) 400 mg for treatment of HIV (NDA 22–145). Briefing document (background package) [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4314b1-01-Merck.pdf [Accessed 2009 Feb 19]
  137. 137.
    Kumar P, Cooper D, Steigbigel R, et al. Efficacy of raltegravir, an HIV integrase inhibitor, in combination with regimens containing-efuvirtide, darunavir, or tipranavir in patients with triple-class resistant virus: combined results from BENCHMRK-1 and BENCHMRK-2 [abstract no. P7.2/06]. 11th European AIDS Conference/EACS; 2007 Oct 24–27; MadridGoogle Scholar
  138. 138.
    Wenning LA, Friedman E, Kost JT, et al. Lack of a significant drug interaction between MK-0518 and tenofovir disoproxil fumarate (TDF) [abstract no. A-375]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco, (CA)Google Scholar
  139. 139.
    Iwamoto M, Wenning L, Petry A, et al. Minimal effects of ritonavir and efavirenz on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother 2008; 52(12): 4338–43PubMedCrossRefGoogle Scholar
  140. 140.
    Iwamoto M, Kassahun K, Troyer MD, et al. Lack of a pharmacokinetic effect of raltegravir on midazolam: in vitro/in vivo correlation. J Clin Pharmacol 2008 Feb; 48(2): 209–14PubMedCrossRefGoogle Scholar
  141. 141.
    Iwamoto M, Wenning LA, Liou SY, et al. Rifampin (RIF) modestly reduces plasma levels of MK-0518 [abstract no. P299]. 8th International Congress on Drug Therapy for HIV; 2006 Nov 12–16; GlasgowGoogle Scholar
  142. 142.
    Anderson MS, Wenning LA, Moreau A, et al. Effect of raltegravir (RAL) on the pharmacokinetics (PK) of oral contraceptives [abstract no. A-1425]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; ChicagoGoogle Scholar
  143. 143.
    PubChem. JTK 303 [elvitegravir] — compound summary (CID 5277135) [online]. Available from URL: http://pubchem.ncbi.nlm.nih.gov.libproxy.lib.unc.edu/summary/summary.cgi?cid=5277135&loc=ec_rcs [Accessed 2009 Feb 19]
  144. 144.
    Ramanathan S, Shen G, Hinkle J, et al. Pharmacokinetics of coadministered ritonavir-boosted elvitegravir and zidovudine, didanosine, stavudine, or abacavir. J Acquir Immune Defic Syndr 2007 Oct 1; 46(2): 160–6PubMedCrossRefGoogle Scholar
  145. 145.
    DeJesus E, Berger D, Markowitz M, et al., for the 183-0101 Study Team. Antiviral activity, pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naïve and treatment-experienced patients. J Acquir Immune Defic Syndr 2006 Sep; 43(1): 1–5PubMedCrossRefGoogle Scholar
  146. 146.
    Kawaguchi I, Ishikawa T, Ishibashi M, et al. Safety and pharmacokinetics of single oral dose of JTK-303/GS-9137, a novel HIV integrase inhibitor, in healthy volunteers. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–9; San Francisco (CA)Google Scholar
  147. 147.
    Mathias A, Hinkle J, Enejosa J, et al. Lack of pharmacokinetic interaction between ritonavir-boosted GS-9137 (elvitegravir) and tipranavir/r [abstract no. TUPDB06]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; SydneyGoogle Scholar
  148. 148.
    Mathias A, Shen G, Enejosa J, et al. Lack of pharmacokinetic interaction between ritonavir-boosted GS-9137 (elvitegravir) and darunavir/r [abstract no. TUPDB03]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; SydneyGoogle Scholar
  149. 149.
    Ziagen® (abacavir sulphate) tablets and oral solution: US prescribing information. Research Triangle Park (NC): GlaxoSmithKline, 2008 Jul [online]. Available from URL: http://us.gsk.com/products/assets/us_ziagen.pdf [Accessed 2009 Mar 27]
  150. 150.
    Retrovir (zidovudine) IV infusion: US prescribing information. Research Triangle Park (NC): GlaxoSmithKline, 2006 [online]. Available from URL: http://us.gsk.com/products/assets/us_retrovir_injection.pdf [Accessed 2009 Feb 19]
  151. 151.
    Ramanathan S, Skillington J, Plummer A, et al. Lack of clinically relevant drug-drug interaction between ritonavir-boosted GS-9137 (GS-9137/r) and emtricitabine (FTC)/ tenofovir disoproxil fumarate (TDF) [abstract no. TUPE0080]. XVI International AIDS Conference; 2006 Aug 13–18; Toronto (ON)Google Scholar
  152. 152.
    Ramanathan S, Lagan K, Plummer A, et al. Pharmacokinetic evaluation of drug interactions with ritonavir-boosted HIV integrase inhibitor GS-9137 (elvitegravir) and acid-reducing agents [abstract no. 69]. 8th International Workshop on Clinical Pharmacology of HIV Therapy; 2007 Apr 16–18; BudapestGoogle Scholar
  153. 153.
    Li F, Goila-Gaur R, Salzwedel K, et al. PA-457: a potent HIV inhibitor that disrupts core condensation by targeting a late step in Gag processing. Proc Natl Acad Sci USA 2003 Nov 11; 100(23): 13555–60PubMedCrossRefGoogle Scholar
  154. 154.
    Martin DE, Blum R, Wilton J, et al. Safety and pharmacokinetics of bevirimat (PA-457), a novel inhibitor of human immunodeficiency virus maturation, in healthy volunteers. Antimicrob Agents Chemother 2007 Sep; 51(9): 3063–6PubMedCrossRefGoogle Scholar
  155. 155.
    Martin DE, Smith P, Wild CT, et al. In vitro and in vivo disposition of PA-457, a novel inhibitor of HIV-1 maturation [abstract no. WePeA5644]. XV International AIDS Conference; 2004 Jul 11–16; BangkokGoogle Scholar
  156. 156.
    Martin DE, Blum R, Doto J, et al. Multiple-dose pharmacokinetics and safety of bevirimat, a novel inhibitor of HIV maturation, in healthy volunteers. Clin Pharmacokinet 2007; 46(7): 589–98PubMedCrossRefGoogle Scholar
  157. 157.
    Martin DE, Smith P, Goila-Gaur R, et al. Determinants of activity, in vitro metabolism and in vivo disposition of the novel maturation inhibitor PA-457 [abstract no. 545]. 11th Conference on Retroviruses and Opportunistic Infections; 2004 Feb 8–11; San Francisco (CA)Google Scholar
  158. 158.
    Smith P, Forrest A, Beatty G, et al. Pharmacokinetics/pharmacodynamics of PA-457 in a 10-day multiple dose monotherapy trial in HIV infected patients [abstract no. 52]. 13th Conference on Retroviruses and Opportunistic Infections; 2006 Feb 5–8; Denver (CO)Google Scholar
  159. 159.
    Martin D, Galbraith H, Ellis C, et al. Minimal effect of ritonavir (RTV) on the pharmacokinetics (PK) of bevirimat (BVM) in healthy volunteers [abstract no. WEPEB015]. 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention; 2007 Jul 22–25; SydneyGoogle Scholar
  160. 160.
    Martin DE, Gailbraith H, Schettler J, et al. Lack of a PK/PD interaction between PA-457 and atazanavir (ATV) in healthy volunteers [abstract no. A-377]. 46th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2006 Sep 27–30; San Francisco (CA)Google Scholar
  161. 161.
    de Béthune M-P, Andries K, Azijn H, et al. TMC278, a new potent NNRTI, with an increased barrier to resistance and good pharmacokinetic profile [abstract no. 556]. 12th Conference on Retroviruses and Opportunistic Infections; 2005 Feb 22–25; Boston (MA)Google Scholar
  162. 162.
    Petry AS, Hanley WD, Silk G, et al. Effect of severe renal insufficiency on raltegravir (RAL) pharmacokinetics [abstract no. A-1424]. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy; 2007 Sep 17–20; Chicago (IL)Google Scholar

Copyright information

© Adis International Limited 2009

Authors and Affiliations

  • Kevin C. Brown
    • 1
  • Sunita Paul
    • 1
  • Angela D. M. Kashuba
    • 1
  1. 1.School of Pharmacy, Center for AIDS Research Clinical Pharmacology and Analytical Chemistry CoreUniversity of North Carolina at Chapel HillChapel HillUSA

Personalised recommendations