Intracellular accumulation of nelfinavir and its relationship to P-glycoprotein expression and function in HIV-infected patients

Antiviral Therapy

Volumn 9, Issue 1, 2004, Pages 115-122

  Hennessy, Martina ^a   Clarke, Susan ^b   Spiers, J Paul ^a   Kelleher, Dermot ^a   Mulcahy, Fiona ^b   Hoggard, Patrick ^c   Back, David ^c   Barry, Michael ^a  

^a TRINITY COLLEGE DUBLIN   (Ireland)

^b ST JAMES S HOSPITAL   (Ireland)

^c UNIVERSITY OF LIVERPOOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEIN P; LAMIVUDINE PLUS ZIDOVUDINE; METHANOL; NELFINAVIR; NUCLEOSIDE ANALOG; RHODAMINE;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CELL ISOLATION; CLINICAL ARTICLE; COMPUTER PROGRAM; CORRELATION ANALYSIS; DENSITY GRADIENT CENTRIFUGATION; DRUG ACCUMULATION; DRUG HALF LIFE; FLOW CYTOMETRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LYMPHOCYTE; MALE; MASS SPECTROMETRY; MEAN RESIDENCE TIME; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION;

AREA UNDER CURVE; FLOW CYTOMETRY; GENES, MDR; HIV INFECTIONS; HIV PROTEASE INHIBITORS; HUMANS; METABOLIC CLEARANCE RATE; NELFINAVIR; P-GLYCOPROTEIN; STATISTICS, NONPARAMETRIC; TISSUE DISTRIBUTION;

EID: 1542288853     PISSN: 13596535     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (44)

1. Ledergerber B, Egger M, Opravil M, Telenti A, Battegay M, Vernazza P, Sudre P, Flepp M, Furrer H, Francioli P & Weber R for the Swiss HIV Cohort Study. Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study. Lancet 1999; 353:863-868.
2. Carpenter CCJ, Cooper DA, Fischl MA, Gatell JM, Gazzard BG, Hammer SM, Hirsch MS, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Saag MS, Schechter M, Schooley RT, Thompson MA, Veller S, Yeni PG & Volberding PA. Antiretroviral therapy in adults. Updated recommendations of the international AIDS society - USA Panel. Journal of the American Medical Association 2000; 283:381-390.
3. Barry M, Mulcahy F, Merry C, Gibbons S & Back D. Pharmacokinetics and potential interactions amongst anti-retroviral agents used to treat patients with HIV infection. Clinical Pharmacokinetics 1999; 36:289-304.
4. Barry MG, Merry C, Lloyd J, Halifax K, Carey P, Mulcahy F & Back DJ. Variability in trough plasma saquinavir concentrations in HIV patients - a case for therapeutic drug monitoring. British Journal of Clinical Pharmacology 1998; 45:501-502.
5. Durant J, Clevenbergh P, Garaffo R, Halfon P, Icard S, Del Giudice P, Montagne N, Schapiro JM & Dellamonica P. The importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic guided therapy: pharmacological data from the Viradapt Study. AIDS 2000; 14:1333-1339.
6. Anderson PL, Brundage RC, Bushman L, Kakuda TN, Remmel RP & Fletcher CV. Indinavir plasma protein binding in HIV-1-infected adults. AIDS 2000; 14:2293-2297.
7. Gieshke R, Fotteler B, Buss N & Steiner J-L. Relationship between exposure to saquinavir monotherapy and antiviral response in HIV-positive patients. Clinical Pharmacokinetics 1999; 37:75-86.
8. Hoetelmans RM, Reijers MHE, Weverling GJ, ten Kate RW, Wit FWNM, Mulder JW, Weigel HM, Frissen PHJ, Roos M, Jurriaans S, Schuitemaker H, de Wolf F, Beijnen JH & Lange JMA. The effect of plasma drug concentrations on HIV-1 clearance rate during quadruple drug therapy. AIDS 1998; 12:F111-F115.
9. Descamps D, Flandre P, Calvez V, Peytavin G, Meiffredy V, Collin G, Delaugerre C, Robert-Delmas S, Bazin B, Aboulker JP, Pialoux G, Raffi F & Brun-Vezinet F. Mechanisms of virologic failure in previously untreated HIV-infected patients from a trial of induction-maintenance therapy. Journal of the American Medical Association 2000; 283:205-211.
10. Murphy RL, Sommadossi JP, Lamson M, Hall DB, Myers M & Dusek A. Antiviral effect and pharmacokinetic interaction between nevirapine and indinavir in persons infected with human immunodeficiency virus type 1. Journal of Infectious Diseases 1999; 179:1116-1123.
11. Burger DM, Hoetelmans RM, Hugen PW, Mulder JW, Meenhorst PL, Koopmans PP, Brinkman K, Keuter M, Dolmans W & Hekster YA. Low plasma concentrations of indinavir are related to virological treatment failure in HIV-1-infected patients on indinavir-containing triple therapy. Antiviral Therapy 1998; 3:215-220.
12. Zhang L, Ramaratam B, Tenner-Racz K, He Y, Vesanen M, Lewin S, Talal A, Racz P, Perelson AS, Korber BT, Markowitz M & Ho DD. Quantifying residual HIV-1 replication receiving combination anti retroviral therapy. New England Journal of Medicine 1999; 340:1605-1613.
13. Condra JH, Schleif WA, Blahy OM, Gabryelski LJ, Graham DJ, Quintero JC, Rhodes A, Robbins HL, Roth E & Shivaprakash M. In vivo emergence of HIV-1 variants resistant to multiple protease inhibitors. Nature 1995; 374:569-571.
14. Jacobsen H, Hanggi M, Ott M, Owen S, Andreoni M, Vella S & Mous J. In vivo resistance to a human immunodeficiency virus type 1 protease inhibitor: mutations, kinetics and frequencies. Journal of Infectious Diseases 1996; 173:1379-1387.
15. 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; 13:1623-1627.
16. Clayette P, Jorjuria S & Dormont D. Significance of P-glycoprotein for the pharmacology and clinical use of HIV protease inhibitors. AIDS 2000; 14:235-236.
17. Huisman T, Smit JW & Schinkel AH. Significance of P-glycoprotein for the pharmacology and clinical use of HIV protease inhibitors. AIDS 2000; 14:237-242.
18. Lee CGL, Gottesman MM, Cardarelli CO, Ramachandra M, Jeang K-T, Ambudkar SV, Pastan I & Dey S. HIV-1 protease inhibitors are substrates for the MDR-1 multidrug transporter. Biochemistry 1998; 37:3594-3601.
19. Coffin JM. Retroviridae and their replication. In Virology. Edited by B Fields. 1991; pp 645-708. New York: Raven Press.
20. Bilello JA, Billello PA, Strellecht J, Leonard D, Norbeck DJ & Kempf T. Human serum alpha 1 acid glycoprotein reduces uptake, intracellular concentration, and antiviral activity of A-80987, an inhibitor of the human immunodeficiency virus type 1 protease. Antimicrobial Agents & Chemotherapy 1996; 40:1491-1497.
21. Nascimbeni M, Lamotte C, Peytavin G, Farinotti R & Clavel F. Kinetics of antiviral activity and intracellular pharmacokinetics of human immunodeficiency virus type 1 protease inhibitors in tissue culture. Antimicrobial Agents & Chemotherapy 2000; 43:2629-2634.
22. Jones K, Hoggard P, Sales SD, Khoo SH, Davey R & Back D. Differences in intracellular accumulation of HIV protease inhibitors in vitro and the effect of active transport. AIDS 2001; 15:675-681.
23. Hennessy M, Clarke S, Spiers JP, Mulcahy F, Kelleher D, Meaden ER, Maher B, Bergin C, Tjia J, Hoggard P, Back D & Barry M. Intracellular indinavir pharmacokinetics in HIV infected patients: comparison with plasma pharmacokinetics. Antiviral Therapy 2003; 8:191-198.
24. Kim RB, Fromm M, Wandel C, Leake B, Wood AJ & Roden DM. The drug transporter P glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. Journal of Clinical Investigation 1998; 101:289-294.
25. Huisman MT, Smit JW, Wiltshire HR, Hoetelmans RM, Beijnen JH & Schinkel AH. P-glycoprotein limits oral availability, brain, and foetal penetration of saquinavir even with high doses of ritonavir. Molecular Pharmacology 2001; 59:806-813.
26. Donahue JP, Dowdy D, Ratnam KK, Hulgan T, Price J, Unutmaz D, Nicotera J, Raffanti S, Becker M & Haas DW. Effects of nelfinavir and its M8 metabolite on lymphocyte P-glycoprotein activity during antiretroviral therapy. Clinical Pharmacology & Therapeutics 2003; 73:78-86.
27. Lucia MB, Rutella S, Leone G, Vella S & Cauda R. HIV-protease inhibitors contribute to P-glycoprotein efflux function defect in peripheral blood lymphocytes from HIV-positive patients receiving HAART. Journal of Acquired Immune Deficiency Syndrome 2001; 27:321-330.
28. Eagling VA, Profit L & Back DJ. Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-1 protease inhibitor saquinavir by grapefruit juice components. British Journal of Clinical Pharmacology 1999; 48:543-552.
29. Meaden ER, Hoggard PG, Newton P, Tjia JF, Aldam D, Cornforth D, Lloyd J, Williams I, Back DJ & Khoo SH. P-glycoprotein and MRP1 expression and reduced ritonavir and saquinavir accumulation in HIV-infected individuals. Journal of Antimicrobial Chemotherapy 2002; 50:583-588.
30. Chaillou S, Durant J, Garaffo R, Georgenthum E, Roptin C, Clevenbergh P, Dunais B, Mondain V, Roger PM & Dellamonica P. Intracellular concentration of protease inhibitors in HIV-1-infected patients: Correlation with MDR-1 gene expression and low dose of ritonavir. HIV Clinical Trials 2002; 3:493-501.
31. Garaffo R, Durant J, Chaillou S & Roptin C. In vitro and in vivo protease inhibitor (PI) kinetics in human cell line expressing or not MDR1. Role of ritonavir (RI) in intracellular PI accumulation. Interscience Conference on Antimicrobial Agents & Chemotherapy. Toronto, Canada, 2000. Abstract 1167.
32. Scheper RJ, Bulte JW, Brakkee JG, Quak JJ, van der Schoot E, Balm AJ, Meijer CJ, Broxterman HJ, Kuiper CM, Lankelma J & Pinedo HM. Monoclonal antibody JSB-1 detects a highly conserved epitope on the P-glycoprotein associated with multi-drug-resistance. International Journal of Cancer 1988; 42:389-394.
33. Scheffer GL, Kool M, Heijn M, de Haas M, Pijnenborg ACLM, Wijnholds J, van Helvoort A, de Jong MC, Hooijberg JH, Mol CAAM, van der Linden M, de Vree JML, van der Valk P, Oude Elferink RP, Brost P & Scheper RJ. Specific detection of multidrug resistance proteins MRP1, MRP2, MRP3, MRP5, and MDR3 P-glycoprotein with a panel of monoclonal antibodies. Cancer Research 2000; 60:5269-5277.
34. Longo R, Bensi L, Vecchi A, Messora C & Sacchi S. P-glycoprotein expression in acute myeloblastic leukaemia analysed by immunocytochemistry and flow cytometry. Leukaemia Lymphoma 1995; 17:121-125.
35. Brotherick I, Shenton BK, Egan M, Cunliffe WE, Browell DA, Lunt LG, Young JR & Higgs MJ. Examination of multidrug resistance in cell lines and primary breast tumours by flow cytometry. European Journal of Cancer 1996; 32A:2334-2341.
36. Hennessy M, Kelleher D, Spiers JP, Barry M, Kavanagh P, Back D, Mulcahy F & Feely J. St John's Wort increases expression of P-glycoprotein: implications for drug interactions. British Journal of Clinical Pharmacology 2002; 53:75-82.
37. Furman PA, Fyfe JA, St Clair MH, Weinhold K, Rideout JL, Freeman GA, Lehrman SN, Bolognesi DP, Broder S & Mitsuya H. Phosphorylation of 3′-azido-3′-deoxythymidine and selective interaction of the 5′-triphosphate with human immunodeficiency virus reverse transcriptase. Proceedings of the National Academy of Science, USA 1986; 83:8333-8337.
38. Herforth C, Stone JA, Jayewardene AL, Blaschke TF, Fang F, Motoya T & Aweeka FT. Determination of nelfinavir free drug concentrations in plasma by equilibrium dialysis and liquid chromatography/tandem mass spectrometry: important factors for method optimisation. European Journal of Pharmaceutical Sciences 2002; 15:185-195.
39. Khoo SH, Hoggard PG, Williams I, Meaden ER, Newton P, Wilkins EG, Smith A, Tjia JF, Lloyd J, Jones K, Beeching N, Carey P, Peters B & Back DJ. Intracellular accumulation of human immunodeficiency virus protease inhibitors. Antimicrobial Agents & Chemotherapy 2002; 46:3228-3235.
40. Shapiro AB, Corder AB & Ling V. P-glycoprotein-mediated Hoechst 33342 transport out of the lipid bilayer. European Journal of Biochemistry 1997; 250:115-121.
41. Eytan GD, Regev R, Oren R & Assaraf YG. The role of passive transbilayer drug movement in multidrug resistance and its modulation. Journal of Biological Chemistry 1996; 271:12897-12902.
42. Synold TW, Dussault I & Forman BM. The orphan nuclear receptor SXR coordinately regulates drug metabolism and efflux. Nature Medicine 2001; 7:584-590.
43. Dussault I, Lin M, Hollister K, Wang EH, Synold TW & Forman BM. Peptide mimetic HIV protease inhibitors are ligands for the orphan receptor SXR. Journal of Biological Chemistry 2001; 276:33309-33312.
44. Jang SH, Wientjes MG & Au JLS. Interdependent effect of P-glycoprotein-mediated drug efflux and intracellular drug binding on intracellular paclitaxel pharmacokinetics: application of computational modeling. Journal of Pharmacology & Experimental Therapeutics 2003; 304:773-780.