nach oben

Clinical Pharmacokinetics

Erschienen in:

17.06.2016 | Review Article

Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors

verfasst von: Anthony T. Podany, Kimberly K. Scarsi, Courtney V. Fletcher

Erschienen in: Clinical Pharmacokinetics | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Dolutegravir (DTG), elvitegravir (EVG) and raltegravir (RAL) are members of the latest class of antiretrovirals (ARVs) that have become available to treat human immunodeficiency virus (HIV) infection: integrase strand transfer inhibitors (INSTIs). INSTIs are potent inhibitors of the HIV integrase enzyme, with protein binding–adjusted concentration inhibiting viral replication by 90/95 % [IC_90/95] values in the low nanogram per millilitre range, and they retain antiviral activity against strains of HIV with acquired resistance to other classes of ARVs. Each of the INSTIs has unique pharmacokinetic/pharmacodynamic properties, influencing its role in clinical use in specific subsets of patients. RAL and DTG have minimal drug–drug interaction profiles, as their metabolism has minimal cytochrome P450 (CYP) involvement. Conversely, EVG metabolism occurs primarily via CYP3A4 and requires pharmacokinetic boosting to achieve systemic exposures amenable to once-daily dosing. EVG and DTG have the added benefit of availability of fixed-dose combination tablets, allowing for convenient and simplified ARV regimens. RAL is the only INSTI to be listed as a preferred agent in the current US perinatal treatment guidelines. All three INSTIs are recommended regimens for treatment-naïve individuals in the US adult and adolescent HIV treatment guidelines. This review summarizes and compares the pharmacokinetics and pharmacodynamics of the INSTIs, and describes specific pharmacokinetic considerations for special patient conditions: hepatic impairment, renal dysfunction, pregnancy and co-infections.

Department of Health and Human Services (DHHS). Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed 9 Feb 2016.

Min S, Sloan L, DeJesus E, Hawkins T, McCurdy L, Song I, et al. Antiviral activity, safety, and pharmacokinetics/pharmacodynamics of dolutegravir as 10-day monotherapy in HIV-1-infected adults. Aids. 2011;25(14):1737–45.CrossRefPubMed

Min S, Song I, Borland J, Chen S, Lou Y, Fujiwara T, et al. Pharmacokinetics and safety of S/GSK1349572, a next-generation HIV integrase inhibitor, in healthy volunteers. Antimicrob Agents Chemother. 2010;54(1):254–8.CrossRefPubMed

Tivicay^® [package insert]. Research Triangle Park: Viiv Healthcare, August 2015.

Song I, Borland J, Chen S, Patel P, Wajima T, Peppercorn A, et al. Effect of food on the pharmacokinetics of the integrase inhibitor dolutegravir. Antimicrob Agents Chemother. 2012;56(3):1627–9.CrossRefPubMedPubMedCentral

Kobayashi M, Yoshinaga T, Seki T, Wakasa-Morimoto C, Brown KW, Ferris R, et al. In vitro antiretroviral properties of S/GSK1349572, a next-generation HIV integrase inhibitor. Antimicrob Agents Chemother. 2011;55(2):813–21.CrossRefPubMed

Weller S, Chen S, Borland J, Savina P, Wynne B, Piscitelli SC. Bioequivalence of a dolutegravir, abacavir, and lamivudine fixed-dose combination tablet and the effect of food. J Acquir Immune Defic Syndr. 2014;66(4):393–8.CrossRefPubMed

Reese MJ, Savina PM, Generaux GT, Tracey H, Humphreys JE, Kanaoka E, et al. In vitro investigations into the roles of drug transporters and metabolizing enzymes in the disposition and drug interactions of dolutegravir, a HIV integrase inhibitor. Drug Metab Dispos. 2013;41(2):353–61.CrossRefPubMed

Castellino S, Moss L, Wagner D, Borland J, Song I, Chen S, et al. Metabolism, excretion, and mass balance of the HIV-1 integrase inhibitor dolutegravir in humans. Antimicrob Agents Chemother. 2013;57(8):3536–46.CrossRefPubMedPubMedCentral

10.

van Lunzen J, Maggiolo F, Arribas JR, Rakhmanova A, Yeni P, Young B, et al. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviral-naive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect Dis. 2012;12(2):111–8. doi:10.1016/S1473-3099(11)70290-0.CrossRefPubMed

11.

Raffi F, Jaeger H, Quiros-Roldan E, Albrecht H, Belonosova E, Gatell JM, et al. Once-daily dolutegravir versus twice-daily raltegravir in antiretroviral-naive adults with HIV-1 infection (SPRING-2 study): 96 week results from a randomised, double-blind, non-inferiority trial. Lancet Infect Dis. 2013;13(11):927–35. doi:10.1016/S1473-3099(13)70257-3.CrossRefPubMed

12.

Zhang J, Hayes S, Sadler BM, Minto I, Brandt J, Piscitelli S, et al. Population pharmacokinetics of dolutegravir in HIV-infected treatment-naive patients. Br J Clin Pharmacol. 2015;80(3):502–14.CrossRefPubMedPubMedCentral

13.

Vitekta^® [package insert]. Foster City: Gilead Sciences, Inc., July 2015.

14.

Stribild^® [package insert]. Foster City: Gilead Sciences, Inc., July 2015.

15.

Genvoya^® [package insert]. Foster City: Gilead Sciences, Inc., November 2015.

16.

Kawaguchi I, Ishikawa T, Ishibashi M, Irie S, Kakee A, editors. Safety and pharmacokinetics of single oral dose of JTK-303/GS-9137, a novel HIV integrase inhibitor, in healthy volunteers. In: 13th conference on retroviruses and opportunistic infections; 2006.

17.

Kearney B, Mathias A, Zhong L, editors. Pharmacokinetics/pharmacodynamics of GS-9137 an HIV integrase inhibitor in treatment-naive and experienced patients. In: International workshop on clinical pharmacology of HIV therapy; 2006.

18.

German P, Warren D, West S, Hui J, Kearney BP. Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancer-containing single-tablet fixed-dose combination regimen for the treatment of HIV. J Acquir Immune Defic Syndr. 2010;55(3):323–9.CrossRefPubMed

19.

DeJesus E, Berger D, Markowitz M, Cohen C, Hawkins T, Ruane P, et al. Antiviral activity, pharmacokinetics, and dose response of the HIV-1 integrase inhibitor GS-9137 (JTK-303) in treatment-naive and treatment-experienced patients. J Acquir Immune Defic Syndr. 2006;43(1):1–5.CrossRefPubMed

20.

German P, Warren D, Wei L, Zhong L, Hui J, Kearney B, editors. Effect of food on pharmacokinetics of elvitegravir, emtricitabine, tenofovir DF and the pharmacoenhancer GS-9350 as a fixed-dose combination tablet. In: 49th Interscience conference on antimicrobial agents and chemotherapy (ICAAC). San Francisco; 2009.

21.

Shiomi M, Matsuki S, Ikeda A, Ishikawa T, Nishino N, Kimura M, et al. Effects of a protein-rich drink or a standard meal on the pharmacokinetics of elvitegravir, cobicistat, emtricitabine and tenofovir in healthy Japanese male subjects: a randomized, three-way crossover study. J Clin Pharmacol. 2014;54(6):640–8.CrossRefPubMed

22.

Patel P, Song I, Borland J, Patel A, Lou Y, Chen S, et al. Pharmacokinetics of the HIV integrase inhibitor S/GSK1349572 co-administered with acid-reducing agents and multivitamins in healthy volunteers. J Antimicrob Chemother. 2011;66(7):1567–72. doi:10.1093/jac/dkr139.CrossRefPubMed

23.

Ramanathan S, Shen G, Hinkle J, Enejosa J, Kearney B, editors. Pharmacokinetic evaluation of drug interactions with ritonavir-boosted HIV integrase inhibitor GS-9137 (elvitegravir) and acid-reducing agents. In: 8th international workshop on clinical pharmacology of HIV therapy; 2007.

24.

Ramanathan S, Wright M, West S, Kearney B, editors. Pharmacokinetics, metabolism, and excretion of ritonavir-boosted GS-9137 (elvitegravir). In: 8th international workshop on clinical pharmacology of HIV therapy; 2007.

25.

Isentress^® [package insert]. Whitehouse Station: Merck & Co., Inc.; February 2015.

26.

Siccardi M, D’Avolio A, Rodriguez-Novoa S, Cuenca L, Simiele M, Baietto L, et al. Intrapatient and interpatient pharmacokinetic variability of raltegravir in the clinical setting. Ther Drug Monit. 2012;34(2):232–5.CrossRefPubMed

27.

Barau C, Furlan V, Yazdanpanah Y, Fagard C, Molina J-M, Taburet A-M, et al. Characterization of binding of raltegravir to plasma proteins. Antimicrob Agents Chemother. 2013;57(10):5147–50.CrossRefPubMedPubMedCentral

28.

Kiser JJ, Bumpass JB, Meditz AL, Anderson PL, Bushman L, Ray M, et al. Effect of antacids on the pharmacokinetics of raltegravir in human immunodeficiency virus-seronegative volunteers. Antimicrob Agents Chemother. 2010;54(12):4999–5003.CrossRefPubMedPubMedCentral

29.

Arab-Alameddine M, Fayet-Mello A, Lubomirov R, Neely M, di Iulio J, Owen A, et al. Population pharmacokinetic analysis and pharmacogenetics of raltegravir in HIV-positive and healthy individuals. Antimicrob Agents Chemother. 2012;56(6):2959–66.CrossRefPubMedPubMedCentral

30.

Brainard DM, Friedman EJ, Jin B, Breidinger SA, Tillan MD, Wenning LA, et al. Effect of low-, moderate-, and high-fat meals on raltegravir pharmacokinetics. J Clin Pharmacol. 2011;51(3):422–7.CrossRefPubMed

31.

Iwamoto M, Wenning L, Petry A, Laethem M, De Smet M, Kost J, et al. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin Pharmacol Ther. 2008;83(2):293–9.CrossRefPubMed

32.

Markowitz M, Morales-Ramirez JO, Nguyen B-Y, Kovacs CM, Steigbigel RT, Cooper DA, 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-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006;43(5):509–15.CrossRefPubMed

33.

Petry A, Wenning L, Laethem M, De Smet M, Kost J, Merschman S et al., editors. Safety, tolerability, and pharmacokinetics after single and multiple doses of MK-0518 in healthy subjects. In: 46th interscience conference on antimicrobial agents and chemotherapy; 2006.

34.

Kassahun K, McIntosh I, Cui D, Hreniuk D, Merschman S, Lasseter K, 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;35(9):1657–63.CrossRefPubMed

35.

Wenning L, Petry A, Kost J, Jin B, Breidinger S, DeLepeleire I, et al. Pharmacokinetics of raltegravir in individuals with UGT1A1 polymorphisms. Clin Pharmacol Ther. 2009;85(6):623–7.CrossRefPubMed

36.

Eron JJ Jr, Rockstroh JK, Reynes J, Andrade-Villanueva J, Ramalho-Madruga JV, Bekker LG, et al. Raltegravir once daily or twice daily in previously untreated patients with HIV-1: a randomised, active-controlled, phase 3 non-inferiority trial. Lancet Infect Dis. 2011;11(12):907–15. doi:10.1016/S1473-3099(11)70196-7.CrossRefPubMed

37.

Rizk ML, Hang Y, Luo W-L, Su J, Zhao J, Campbell H, et al. Pharmacokinetics and pharmacodynamics of once-daily versus twice-daily raltegravir in treatment-naive HIV-infected patients. Antimicrob Agents Chemother. 2012;56(6):3101–6.CrossRefPubMedPubMedCentral

38.

Debinski HS, Lee CS, Danks JA, Mackenzie PI, Desmond PV. Localization of uridine 5′-diphosphate-glucuronosyltransferase in human liver injury. Gastroenterology. 1995;108(5):1464–9.CrossRefPubMed

39.

Furlan V, Demirdjian S, Bourdon O, Magdalou J, Taburet AM. Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers. J Pharmacol Exp Ther. 1999;289(2):1169–75.PubMed

40.

George J, Murray M, Byth K, Farrell GC. Differential alterations of cytochrome P450 proteins in livers from patients with severe chronic liver disease. Hepatology (Baltimore, Md). 1995;21(1):120–8.

41.

US Food and Drug Administration. Pharmacokinetics in patients with impaired hepatic function: study design, data analysis and impact on dosing and labeling. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm072123.pdf. Accessed 5 March 2016.

42.

US Food and Drug Administration. Dolutegravir. 2013. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2013/204790Orig1s000ClinPharmR.pdf. Accessed 18 Feb 2016.

43.

Song IH, Borland J, Savina PM, Chen S, Patel P, Wajima T, et al. Pharmacokinetics of single-dose dolutegravir in HIV-seronegative subjects with moderate hepatic impairment compared to healthy matched controls. Clin Pharmacol Drug Dev. 2013;2(4):342–8. doi:10.1002/cpdd.55.CrossRefPubMedPubMedCentral

44.

US Food and Drug Administration. Elvitegravir. 2011. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/203100Orig1s000ClinPharmR.pdf. Accessed 18 Feb 2016.

45.

Custodio JM, Rhee M, Shen G, Ling KH, Kearney BP, Ramanathan S. Pharmacokinetics and safety of boosted elvitegravir in subjects with hepatic impairment. Antimicrob Agents Chemother. 2014;58(5):2564–9. doi:10.1128/aac.02180-13.CrossRefPubMedPubMedCentral

46.

Iwamoto M, Hanley WD, Petry AS, Friedman EJ, Kost JT, Breidinger SA, et al. Lack of a clinically important effect of moderate hepatic insufficiency and severe renal insufficiency on raltegravir pharmacokinetics. Antimicrob Agents Chemother. 2009;53(5):1747–52. doi:10.1128/aac.01194-08.CrossRefPubMedPubMedCentral

47.

Calza L, Danese I, Colangeli V, Manfredi R, Magistrelli E, Verucchi G, et al. Plasma concentrations of efavirenz, darunavir/ritonavir and raltegravir in HIV-HCV-coinfected patients without liver cirrhosis in comparison with HIV-monoinfected patients. Infect Dis (London, England). 2015;47(9):625–36. doi:10.3109/23744235.2015.1034169.

48.

Hernandez-Novoa B, Moreno A, Perez-Elias MJ, Quereda C, Dronda F, Casado JL, et al. Raltegravir pharmacokinetics in HIV/HCV-coinfected patients with advanced liver cirrhosis (Child-Pugh C). J Antimicrob Chemother. 2014;69(2):471–5. doi:10.1093/jac/dkt386.CrossRefPubMed

49.

Barau C, Braun J, Vincent C, Haim-Boukobza S, Molina JM, Miailhes P, et al. Pharmacokinetic study of raltegravir in HIV-infected patients with end-stage liver disease: the LIVERAL-ANRS 148 study. Clin Infect Dis. 2014;59(8):1177–84. doi:10.1093/cid/ciu515.CrossRefPubMed

50.

US Food and Drug Administration. Pharmacokinetics in patients with impaired renal function: study design, data analysis and impact on dosing and labeling. March 2010. http://www.fda.gov/downloads/Drugs/…/Guidances/UCM204959.pdf. Accessed 7 March 2016.

51.

Weller S, Borland J, Chen S, Johnson M, Savina P, Wynne B, et al. Pharmacokinetics of dolutegravir in HIV-seronegative subjects with severe renal impairment. Eur J Clin Pharmacol. 2014;70(1):29–35. doi:10.1007/s00228-013-1590-9.CrossRefPubMed

52.

Pozniak A, Arribas JR, Gathe J, Gupta SK, Post FA, Bloch M, et al. Switching to tenofovir alafenamide, coformulated with elvitegravir, cobicistat, and emtricitabine, in HIV-infected patients with renal impairment: 48 week results from a single-arm, multi-center, open-label, phase 3 study. J Acquir Immune Defic Syndr. 2015;. doi:10.1097/qai.0000000000000908.

53.

Molto J, Sanz-Moreno J, Valle M, Cedeno S, Bonal J, Bouarich H, et al. Minimal removal of raltegravir by hemodialysis in HIV-infected patients with end-stage renal disease. Antimicrob Agents Chemother. 2010;54(7):3047–8. doi:10.1128/AAC.00363-10.CrossRefPubMedPubMedCentral

54.

Giguere P, la Porte C, Zhang G, Cameron B. Pharmacokinetics of darunavir, etravirine and raltegravir in an HIV-infected patient on haemodialysis. Aids. 2009;23(6):740–2. doi:10.1097/QAD.0b013e328328f79d.CrossRefPubMed

55.

Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. Available at http://aidsinfo.nih.gov/contentfiles/lvguidelines/PerinatalGL.pdf. Accessed 8 March 2016.

56.

Colbers A, Greupink R, Burger D. Pharmacological considerations on the use of antiretrovirals in pregnancy. Curr Opin Infect Dis. 2013;26(6):575–88. doi:10.1097/QCO.0000000000000017.CrossRefPubMed

57.

Jeong H, Choi S, Song JW, Chen H, Fischer JH. Regulation of UDP-glucuronosyltransferase (UGT) 1A1 by progesterone and its impact on labetalol elimination. Xenobiotica. 2008;38(1):62–75. doi:10.1080/00498250701744633.CrossRefPubMedPubMedCentral

58.

McCormack SA, Best BM. Protecting the fetus against HIV infection: a systematic review of placental transfer of antiretrovirals. Clin Pharmacokinet. 2014;53(11):989–1004. doi:10.1007/s40262-014-0185-7.CrossRefPubMedPubMedCentral

59.

Mulligan N, Best BM, Capparelli E, Stek A, Barr E, Smith E, Chakhtoura N, Wang J, Burchett S, Mirochnick M. Dolutegravir pharmacokinetics in HIV-infected pregnant and postpartum women. CROI 2016. Boston; February 22–25, 2016. Abstract #438.

60.

Schalkwijk S, Colbers A, Konopnicki D, Greupink R, Russel FG, Burger D, et al. First reported use of elvitegravir and cobicistat during pregnancy. AIDS. 2016;30(5):807–8. doi:10.1097/QAD.0000000000000976.CrossRefPubMed

61.

DeJesus E, Rockstroh JK, Henry K, Molina JM, Gathe J, Ramanathan S, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate versus ritonavir-boosted atazanavir plus co-formulated emtricitabine and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3, non-inferiority trial. Lancet. 2012;379(9835):2429–38. doi:10.1016/S0140-6736(12)60918-0.CrossRefPubMed

62.

Watts DH, Stek A, Best BM, Wang J, Capparelli EV, Cressey TR, et al. Raltegravir pharmacokinetics during pregnancy. J Acquir Immune Defic Syndr. 2014;67(4):375–81. doi:10.1097/qai.0000000000000318.CrossRefPubMedPubMedCentral

63.

Blonk MI, Colbers AP, Hidalgo-Tenorio C, Kabeya K, Weizsacker K, Haberl AE, et al. Raltegravir in HIV-1-infected pregnant women: pharmacokinetics, safety, and efficacy. Clin Infect Dis. 2015;61(5):809–16. doi:10.1093/cid/civ366.CrossRefPubMed

64.

Rizk ML, Hang Y, Luo WL, Su J, Zhao J, Campbell H, et al. Pharmacokinetics and pharmacodynamics of once-daily versus twice-daily raltegravir in treatment-naive HIV-infected patients. Antimicrob Agents Chemother. 2012;56(6):3101–6. doi:10.1128/AAC.06417-11.CrossRefPubMedPubMedCentral

65.

Grinsztejn B, De Castro N, Arnold V, Veloso VG, Morgado M, Pilotto JH, et al. Raltegravir for the treatment of patients co-infected with HIV and tuberculosis (ANRS 12 180 REFLATE TB): a multicentre, phase 2, non-comparative, open-label, randomised trial. Lancet Infect Dis. 2014;14(6):459–67.CrossRefPubMed

66.

Burger DM, Magis-Escurra C, van den Berk GE, Gelinck LB. Pharmacokinetics of double-dose raltegravir in two patients with HIV infection and tuberculosis. AIDS. 2010;24(2):328–30.CrossRefPubMed

67.

68.

Clotet B, Feinberg J, van Lunzen J, Khuong-Josses MA, Antinori A, Dumitru I, et al. Once-daily dolutegravir versus darunavir plus ritonavir in antiretroviral-naive adults with HIV-1 infection (FLAMINGO): 48 week results from the randomised open-label phase 3b study. Lancet. 2014;383(9936):2222–31. doi:10.1016/S0140-6736(14)60084-2.CrossRefPubMed

69.

Cahn P, Pozniak AL, Mingrone H, Shuldyakov A, Brites C, Andrade-Villanueva JF, et al. Dolutegravir versus raltegravir in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV: week 48 results from the randomised, double-blind, non-inferiority SAILING study. Lancet. 2013;382(9893):700–8. doi:10.1016/S0140-6736(13)61221-0.CrossRefPubMed

70.

Castagna A, Maggiolo F, Penco G, Wright D, Mills A, Grossberg R, et al. Dolutegravir in antiretroviral-experienced patients with raltegravir- and/or elvitegravir-resistant HIV-1: 24-week results of the phase III VIKING-3 study. J Infect Dis. 2014;210(3):354–62. doi:10.1093/infdis/jiu051.CrossRefPubMedPubMedCentral

71.

72.

Zolopa AR, Berger DS, Lampiris H, Zhong L, Chuck SL, Enejosa JV, et al. Activity of elvitegravir, a once-daily integrase inhibitor, against resistant HIV type 1: results of a phase 2, randomized, controlled, dose-ranging clinical trial. J Infect Dis. 2010;201(6):814–22. doi:10.1086/650698.CrossRefPubMed

73.

Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, et al. Co-formulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus co-formulated efavirenz, emtricitabine, and tenofovir for initial treatment of HIV-1 infection: a randomised, double-blind, phase 3 trial, analysis of results after 48 weeks. Lancet. 2012;379(9835):2439–48. doi:10.1016/S0140-6736(12)60917-9.CrossRefPubMed

74.

US Food and Drug Administration. Raltegravir. 2007. Part 1. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022145_ClinPharmR_P1.pdf. Part 2. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2007/022145_ClinPharmR_P2.pdf. Accessed 18 Feb 2016.

75.

Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, et al. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008;359(4):339–54. doi:10.1056/NEJMoa0708975.CrossRefPubMed

76.

Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, 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-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006;43(5):509–15. doi:10.1097/QAI.0b013e31802b4956.CrossRefPubMed

77.

Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, et al. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007;369(9569):1261–9. doi:10.1016/S0140-6736(07)60597-2.CrossRefPubMed

78.

Fletcher CV. Drug interactions should be evaluated in patients. Clin Pharmacol Ther. 2010;88(5):585–7. doi:10.1038/clpt.2010.213.CrossRefPubMed

79.

Fletcher CV. Editorial commentary: cerebrospinal fluid inhibitory quotients of antiretroviral drugs. Clin Infect Dis. 2015;60(2):318–20. doi:10.1093/cid/ciu775.CrossRefPubMed

80.

US Food and Drug Administration. Guidance for industry, antiviral product development, conducting and submitting virology studies to the agency. 2006. http://www.fda.gov/OHRMS/DOCKETS/98fr/05d-0183-gdl0002-01.pdf. Accessed 18 Feb 2016.

81.

Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, et al. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009;374(9692):796–806. doi:10.1016/S0140-6736(09)60918-1.CrossRefPubMed

82.

Walmsley SL, Antela A, Clumeck N, Duiculescu D, Eberhard A, Gutierrez F, et al. Dolutegravir plus abacavir–lamivudine for the treatment of HIV-1 infection. N Engl J Med. 2013;369(19):1807–18. doi:10.1056/NEJMoa1215541.CrossRefPubMed

83.

Raffi F, Rachlis A, Stellbrink HJ, Hardy WD, Torti C, Orkin C, et al. Once-daily dolutegravir versus raltegravir in antiretroviral-naive adults with HIV-1 infection: 48 week results from the randomised, double-blind, non-inferiority SPRING-2 study. Lancet. 2013;381(9868):735–43. doi:10.1016/S0140-6736(12)61853-4.CrossRefPubMed

84.

Simoni JM, Nance RM, Delaney JAC, Wilson I, Aunon F, Safren SA, et al. HIV viral load in US clinics over time: trends and predictions from CNICS. Conference on retroviruses and opportunistic infections (CROI). February 22, 2016; Boston.

Titel: Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors
verfasst von: Anthony T. Podany
Kimberly K. Scarsi
Courtney V. Fletcher
Publikationsdatum: 17.06.2016
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 1/2017
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.1007/s40262-016-0424-1

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Comparative Clinical Pharmacokinetics and Pharmacodynamics of HIV-1 Integrase Strand Transfer Inhibitors

Abstract

Live-Webinar "Chronische Unterbauch- und Viszeralschmerzen in der Praxis managen"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2017

Modeling the Relationship Between Exposure to Abiraterone and Prostate-Specific Antigen Dynamics in Patients with Metastatic Castration-Resistant Prostate Cancer

Effect of Age and Renal Function on Idarucizumab Pharmacokinetics and Idarucizumab-Mediated Reversal of Dabigatran Anticoagulant Activity in a Randomized, Double-Blind, Crossover Phase Ib Study

Open Flow Microperfusion as a Dermal Pharmacokinetic Approach to Evaluate Topical Bioequivalence

Erratum to: Open Flow Microperfusion as a Dermal Pharmacokinetic Approach to Evaluate Topical Bioequivalence

Population Pharmacokinetics of Paritaprevir, Ombitasvir, and Ritonavir in Japanese Patients with Hepatitis C Virus Genotype 1b Infection

Lithium in Paediatric Patients with Bipolar Disorder: Implications for Selection of Dosage Regimens via Population Pharmacokinetics/Pharmacodynamics