Effects of nelfinavir and its M8 metabolite on lymphocyte P-glycoprotein activity during antiretroviral therapy

Clinical Pharmacology and Therapeutics

Volumn 73, Issue 1, 2003, Pages 78-86

  Donahue, John P ^a,b   Dowdy, David ^a,b   Ratnam, Krishna K ^a,b   Hulgan, Todd ^a,b   Price, James ^a,b   Unutmaz, Derya ^a,b   Nicotera, Janet ^a,b   Raffanti, Steven ^a,b   Becker, Mark ^a,b   Haas, David W ^a,b  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b AGOURON PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DRUG METABOLITE; GLYCOPROTEIN P; HYDROXY TERT BUTYLAMIDE; NELFINAVIR; UNCLASSIFIED DRUG;

ADULT; ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG EFFECT; DRUG INHIBITION; DRUG MECHANISM; DRUG PENETRATION; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MALE; PRIORITY JOURNAL; T LYMPHOCYTE;

ADULT; CD4-POSITIVE T-LYMPHOCYTES; CD8-POSITIVE T-LYMPHOCYTES; FEMALE; HIV PROTEASE INHIBITORS; HIV SEROPOSITIVITY; HUMANS; MALE; NELFINAVIR; P-GLYCOPROTEIN; T-LYMPHOCYTES;

EID: 0037258996     PISSN: 00099236     EISSN: None     Source Type: Journal    
DOI: 10.1067/mcp.2003.11     Document Type: Article

References (34)

1. Schinkel AH, Mayer U, Wagenaar E, Mol CA, van Deemter L, Smit JJ, et al. Normal viability and altered pharmacokinetics in mice lacking mdr1-type (drug-transporting) P-glycoproteins. Proc Natl Acad Sci U S A 1997;94:4028-33.
2. Lee CG, Gottesman MM, Cardarelli CO, Ramachandra M, Jeang KT, Ambudkar SV, et al. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry 1998;37:3594-601.
3. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, Roden DM, et al. The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998;101:289-94.
4. Delforge M-L, Farber C-M, De Leener F, Caroyer J-M, Liesnard C, Van Vooren J-P. Foscarnet activity on human immunodeficiency virus type i in the central nervous system. Clin Infect Dis 1999;28:931.
5. Haas DW, Stone J, Clough LA, Johnson B, Spearman P, Harris VL, et al. Steady-state pharmacokinetics of indinavir in cerebrospinal fluid and plasma among adults with human immunodeficiency virus type 1 infection. Clin Pharmacol Ther 2000;68:367-74.
6. Gisolf EH, Enting RH, Jurriaans S, de Wolf F, Van der Ende ME, Hoetelmans RM, et al. Cerebrospinal fluid HIV-1 RNA during treatment with ritonavir/saquinavir or ritonavir/saquinavir/stavudine. AIDS 2000;14:1583-9.
7. Choo EF, Leake B, Wandel C, Imamura H, Wood AJ, Wilkinson GR, et al. Pharmacological inhibition of P-glycoprotein transport enhances the distribution of HIV-1 protease inhibitors into brain and testes. Drug Metab Dispos 2000;28:655-60.
8. Chaudhary PM, Mechetner EB, Roninson IB. Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes. Blood 1992;80: 2735-9.
9. Srinivas RV, Middlemas D, Flynn P, Fridland A. Human immunodeficiency virus protease inhibitors serve as substrates for multidrug transporter proteins MDR1 and MRP 1 but retain antiviral efficacy in cell lines expressing these transporters. Antimicrob Agents Chemother 1998; 42:3157-62.
10. Klimecki WT, Futscher BW, Grogan TM, Dalton WS. P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood 1994;83: 2451-8.
11. Powderly WG, Tebas P. Nelfinavir, a new protease inhibitor: early clinical results. AIDS 1999;13(Suppl 1): S41-8.
12. Bardsley-Elliot A, Plosker GL. Nelfinavir: an update on its use in HIV infection. Drugs 2000;59:581-620.
13. Zhang KE, Wu E, Patick AK, Kerr B, Zorbas M, Lankford A, et al. Circulating metabolites of the human immunodeficiency virus protease inhibitor nelfinavir in humans: structural identification, levels in plasma, and antiviral activities. Antimicrob Agents Chemother 2001; 45:1086-93.
14. 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. Br J Clin Pharmacol 1999;48:543-52.
15. Huisman MT, Smit JW, Wiltshire HR, Hoetelmans RM, Beijnen JH, Schinkel AH. P-glycoprotein limits oral availability, brain, and fetal penetration of saquinavir even with high doses of ritonavir. Mol Pharmacol 2001; 59:806-13.
16. Polli JW, Jarrett JL, Studenberg SD, Humphreys JE, Dennis SW, Brouwer KR, et al. Role of P-glycoprotein on the CNS disposition of amprenavir (141W94), an HIV protease inhibitor. Pharm Res 1999;16:1206-12.
17. Washington CB, Wiltshire HR, Man M, Moy T, Harris SR, Worth E, et al. The disposition of saquinavir in normal and P-glycoprotein deficient mice, rats, and in cultured cells. Drug Metab Dispos 2000;28:1058-62.
18. Drewe J, Gutmann H, Fricker G, Torok M, Berlinger C, Huwyler J. HIV protease inhibitor ritonavir: a more potent inhibitor of P-glycoprotein than the cyclosporine analog SDZ PSC 833. Biochem Pharmacol 1999;57: 1147-52.
19. Gutmann H, Fricker G, Drewe J, Toeroek M, Miller DS. Interactions of HIV protease inhibitors with ATP-dependent drug export proteins. Mol Pharmacol 1999;56: 383-9.
20. Washington CB, Duran GE, Man MC, Sikic BI, Blaschke TF. Interaction of anti-HIV protease inhibitors with the multidrug transporter P-glycoprotein (P-gp) in human cultured cells. J Acquir Immune Defic Syndr 1998;19: 203-9.
21. Hochman JH, Chiba M, Yamazaki M, Tang C, Lin JH. P-glycoprotein-mediated efflux of indinavir metabolites in Caco-2 cells expressing cytochrome P450 3A4. J Pharmacol Exp Ther 2001;298:323-30.
22. Hochman JH, Chiba M, Nishime J, Yamazaki M, Lin JH. Influence of P-glycoprotein on the transport and metabolism of indinavir in Caco-2 cells expressing cytochrome P-450 3A4. J Pharmacol Exp Ther 2000;292:310-8.
23. Kim AE, Dintaman JM, Waddell DS, Silverman JA. Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther 1998;286:1439-45.
24. 2(3) is not a substrate for multidrug resistance protein (MRP)-mediated drug efflux. Cytometry 1996;25:14-20.
25. Haas DW, Johnson B, Nicotera J, Bailey DG, Harris VL, Bowles F, et al. Steady-state indinavir pharmacokinetics in cerebrospinal fluid and plasma in patients receiving low-dose ritonavir, as determined by ultra-intensive CSF sampling. In: Proceedings of the Ninth Conference on Retroviruses and Opportunistic Infections; 2002 Feb 25-28; Seattle, Washington. Seattle: The Conference; 2002.
26. Stewart A, Steiner J, Mellows G, Laguda B, Norris D, Bevan P. Phase I trial of XR9576 in healthy volunteers demonstrates modulation of P-glycoprotein in CD56+ lymphocytes after oral and intravenous administration. Clin Cancer Res 2000;6:4186-91.
27. Fromm MF, Kim RB, Stein CM, Wilkinson GR, Roden DM. Inhibition of P-glycoprotein-mediated drug transport: a unifying mechanism to explain the interaction between digoxin and quinidine. Circulation 1999;99:552-57.
28. Huang L, Wring SA, Woolley JL, Brouwer KR, Serabjit-Singh C, Polli JW. Induction of P-glycoprotein and cytochrome P450 3A by HIV protease inhibitors. Drug Metab Dispos 2001;29:754-60.
29. Perloff MD, von Moltke LL, Fahey JM, Daily JP, Greenblatt DJ. Induction of P-glycoprotein expression by HIV protease inhibitors in cell culture. AIDS 2000; 14:1287-9.
30. Becquemont L, Camus M, Eschwege V, Barbu V, Rey E, Funck-Brentano C, et al. Lymphocyte P-glycoprotein expression and activity before and after rifampicin in man. Fundam Clin Pharmacol 2000;14:519-25.
31. Mu XY, Gosland MP, Bartik MM, Schimmelpfennig J, Kay NE. Activation of human peripheral blood T cells does not lead to increased P-glycoprotein expression. J Clin Immunol 1999;19:239-46.
32. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmoller J, Johne A, et al. Functional polymorphisms of the human multidrug-resistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A 2000;97:3473-8.
33. Kim RB, Leake BF, Choo EF, Dresser GK, Kubba SV, Schwarz UI, et al. Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 2001;70:189-99.
34. Pai VB, Nahata MC. Nelfinavir mesylate: a protease inhibitor. Ann Pharmacother 1999;33:325-39.