Evaluation of the effect of cobicistat on the in vitro renal transport and cytotoxicity potential of tenofovir

Antimicrobial Agents and Chemotherapy

Volumn 57, Issue 10, 2013, Pages 4982-4989

  Stray, Kirsten M ^a   Bam, Rujuta A ^a   Birkus, Gabriel ^a   Hao, Jia ^a   Lepist, Eve Irene ^a   Yant, Stephen R ^a   Ray, Adrian S ^a   Cihlar, Tomas ^a  

^a GILEAD SCIENCES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COBICISTAT; ELVITEGRAVIR; EMTRICITABINE; MEMBRANE PROTEIN; MULTIDRUG AND TOXIN EXTRUSION PROTEIN 1; MULTIDRUG RESISTANCE PROTEIN 4; OCTAMER TRANSCRIPTION FACTOR 2; ORGANIC ANION TRANSPORTER 1; ORGANIC ANION TRANSPORTER 3; PROBENECID; RITONAVIR; TENOFOVIR; UNCLASSIFIED DRUG;

ARTICLE; CELL CULTURE; CELL ISOLATION; CONTROLLED STUDY; CYTOTOXICITY; DRUG EFFECT; DRUG INHIBITION; DRUG POTENTIATION; DRUG SENSITIVITY; DRUG TRANSPORT; HUMAN; HUMAN CELL; HUMAN TISSUE; IC 50; IN VITRO STUDY; KIDNEY CELL; KIDNEY CORTEX; KIDNEY PARENCHYMA; KIDNEY PROXIMAL TUBULE; KIDNEY PROXIMAL TUBULE CELL; KIDNEY TUBULE ABSORPTION; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION;

ADENINE; ADULT; ANTI-HIV AGENTS; CARBAMATES; CELL LINE; DRUG INTERACTIONS; HUMANS; KIDNEY; MALE; MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS; ORGANIC ANION TRANSPORT PROTEIN 1; ORGANIC ANION TRANSPORTERS, SODIUM-INDEPENDENT; ORGANIC CATION TRANSPORT PROTEINS; ORGANOPHOSPHONATES; THIAZOLES;

EID: 84884277618     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00712-13     Document Type: Article

References (32)

1. Xu L, Liu H, Murray BP, Callebaut C, Lee MS, Hong A, Strickley R, Tsai L, Stray K, Wang Y, Rhodes GR, Desai MC. 2010. Cobicistat (GS-9350): a potent and selective inhibitor of human CYP3A as a novel pharmacoenhancer. ACS Med. Chem. Lett. 1:209-213.
2. Mathias AA, German P, Murray BP, Wei L, Jain A, West S, Warren D, Hui J, Kearney BP. 2010. Pharmacokinetics and pharmacodynamics of GS-9350: a novel pharmacokinetic enhancer without anti-HIV activity. Clin. Pharmacol. Ther. 87:322-329.
3. Ramanathan S, Mathias AA, German P, Kearney BP. 2011. Clinical pharmacokinetic and pharmacodynamic profile of the HIV integrase inhibitor elvitegravir. Clin. Pharmacokinet. 50:229-244.
4. Gallant J, Koenig E, Andrade-Villanueva J, Chetchotisakd P, DeJesus E, Antunes F, Arastéh K, Moyle G, Rizzardini G, Fehr J, Liu Y, Zhong L, Callebaut C, Ramanathan S, Szwarcberg J, Rhee M, Cheng A. 2012. Cobicistat versus ritonavir as pharmacoenhancers in combination with atazanavir plus tenofovirDF/emtricitabine: phase 3 randomized, double blind, active-controlled trial, week 48 results. J. Int. AIDS Soc. 15(Suppl 3):53.
5. Sax PE, DeJesus E, Mills A, Zolopa A, Cohen C, Wohl D, Gallant JE, Liu HC, Zhong L, Yale K, White K, Kearney BP, Szwarcberg J, Quirk E, Cheng AK. 2012. 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 379:2439-2448.
6. Zolopa A, Sax PE, DeJesus E, Mills A, Cohen C, Wohl D, Gallant JE, Liu HC, Plummer A, White KL, Cheng AK, Rhee MS, Szwarcberg J. 2013. A randomized double-blind comparison of coformulated elvitegravir/ cobicistat/emtricitabine/ tenofovir disoproxil fumarate versus efavirenz/ emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: analysis of week 96 results. J. Acquir. Immune Defic. Syndr. 63:96-100.
7. DeJesus E, Rockstroh JK, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Yale K, Szwarcberg J, White K, Cheng AK, Kearney BP. 2012. 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 379:2429-2438.
8. Lepist EI, Phan TK, Roy A, Tong L, Maclennan K, Murray B, Ray AS. 2012. Cobicistat boosts the intestinal absorption of transport substrates, including HIV protease inhibitors and GS-7340, in vitro. Antimicrob. Agents Chemother. 56:5409-5413.
9. Rockstroh JK, DeJesus E, Henry K, Molina JM, Gathe J, Ramanathan S, Wei X, Plummer A, Abram M, Cheng AK, Fordyce MW, Szwarcberg J. 2013. A randomized, double-blind comparison of coformulated elvitegravir/ cobicistat/emtricitabine/ tenofovir DF vs ritonavir-boosted atazanavir plus coformulated emtricitabine and tenofovir DF for initial treatment of HIV-1 infection: analysis of week 96 results. J. Acquir. Immune Defic. Syndr. 62:483-486.
10. German P, Liu HC, Szwarcberg J, Hepner M, Andrews J, Kearney BP, Mathias A. 2012. Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function. J. Acquir. Immune Defic. Syndr. 61:32-40.
11. Cihlar T, Ho ES, Lin DC, Mulato AS. 2001. Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs. Nucleosides Nucleotides Nucleic Acids 20:641-648.
12. Kearney BP, Flaherty JF, Shah J. 2004. Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics. Clin. Pharmacokinet. 43: 595-612.
13. Ray AS, Cihlar T, Robinson KL, Tong L, Vela JE, Fuller MD, Wieman LM, Eisenberg EJ, Rhodes GR. 2006. Mechanism of active renal tubular efflux of tenofovir. Antimicrob. Agents Chemother. 50:3297-3304.
14. Rodriguez-Novoa S, Alvarez E, Labarga P, Soriano V. 2010. Renal toxicity associated with tenofovir use. Expert Opin. Drug Saf. 9:545-559.
15. Barditch-Crovo P, Deeks SG, Collier A, Safrin S, Coakley DF, Miller M, Kearney BP, Coleman RL, Lamy PD, Kahn JO, McGowan I, Lietman PS. 2001. Phase I/II trial of the pharmacokinetics, safety, and antiretroviral activity of tenofovir disoproxil fumarate in HIV-1 infected adults. Antimicrob. Agents Chemother. 45:2733-2739.
16. Imaoka T, Kusuhara H, Adachi M, Schuetz JD, Takeuchi K, Sugiyama Y. 2007. Functional involvement of multidrug resistance associated protein 4 (MRP4/ABCC4) in the renal elimination of the anti-viral drugs, adefovir and tenofovir. Mol. Pharmacol. 71:619-627.
17. Cihlar T, Bleasby K, Roy A, Pritchard J. 2004. Antiviral acyclic nucleotide analogs tenofovir and adefovir are substrates for human kidney organic anion, but not cation transporters: implications for potential renal drug interactions, poster A-443. Abstr. 44th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
18. Lepist E-I, Murray BP, Tong L, Roy A, Bannister R, Ray AS. 2011. Effect of cobicistat and ritonavir on proximal renal tubular cell uptake and efflux transporters, abstr A1-1724. Abstr. 51st Intersci. Conf. Antimicrob. Agents Chemother., Chicago, IL. American Society for Microbiology, Washington, DC.
19. Cihlar T, Ray A, Laflamme G, Vella J, Tong L, Fuller M, Roy A, Rhodes G. 2007. Molecular assessment of the potential for renal drug interactions between tenofovir and HIV protease inhibitors. Antivir Ther. 12:267-272.
20. Boffito M, Back DJ, Blaschke TF, Rowland M, Bertz RJ, Gerber JG, Miller V. 2003. Protein binding in antiretroviral therapies. AIDS Res. Hum. Retroviruses 19:825-835.
21. Acosta EP, Limoli KL, Trinh L, Parkin NT, King JR, Weidler JM, Ofotokun I, Petropoulos CJ. 2012. Novel method to assess antiretroviral target trough concentrations using in vitro susceptibility data. Antimicrob. Agents Chemother. 56:5938-5945.
22. Wittwer MB, Zur AA, Khuri N, Kido Y, Kosaka A, Zhang X, Morrissey KM, Sali A, Huang Y, Giacomini KM. 2013. Discovery of potent, selective multidrug and toxin extrusion transporter 1 (MATE1, SLC47A1) inhibitors through prescription drug profiling and computational modeling. J. Med. Chem. 56:781-795.
23. Richman DD. 2001. Antiretroviral activity of emtricitabine, a potent nucleoside reverse transcriptase inhibitor. Antivir. Ther. 6:83-88.
24. Cihlar T, Birkus G, Greenwalt DE, Hitchcock MJM. 2002. Tenofovir exhibits low cytotoxicity in various human cell types: comparison with other nucleoside reverse transcriptase inhibitors. Antivir. Res. 54:37-45.
25. Vidal F, Domingo JC, Guallar J, Saumoy M, Cordobilla B, Sanchez de la Rosa R, Giralt M, Alvarez ML, Lopez-Dupla M, Torres F, Villarroya F, Cihlar T, Domingo P. 2006. In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells. Antimicrob. Agents Chemother. 50:3824-3832.
26. Cihlar T, Laflamme G, Fisher R, Carey AC, Vela JE, Mackman R, Ray AS. 2009. Novel nucleotide human immunodeficiency virus reverse transcriptase inhibitor GS-9148 with a low nephrotoxic potential: characterization of renal transport and accumulation. Antimicrob. Agents Chemother. 53:150-156.
27. van Lunzen J, Maggiolo F, Arribas JR, Rakhmanova A, Yeni P, Young B, Rockstroh JK, Almond S, Song I, Brothers C, Min S. 2012. Once daily dolutegravir (S/GSK1349572) in combination therapy in antiretroviralnaive adults with HIV: planned interim 48 week results from SPRING-1, a dose-ranging, randomised, phase 2b trial. Lancet Infect. Dis. 12:111-118.
28. van Acker BA, Koomen GC, Koopman MG, de Waart DR, Arisz L. 1992. Creatinine clearance during cimetidine administration for measurement of glomerular filtration rate. Lancet 340:1326-1329.
29. Pushpakom SP, Liptrott NJ, Rodriguez-Novoa S, Labarga P, Soriano V, Albalater M, Hopper-Borge E, Bonora S, Di Perri G, Back DJ, Khoo S, Pirmohamed M, Owen A. 2011. Genetic variants of ABCC10, a novel tenofovir transporter, are associated with kidney tubular dysfunction. J. Infect. Dis. 204:145-153.
30. Kohler JJ, Hosseini SH, Green E, Abuin A, Ludaway T, Russ R, Santoianni R, Lewis W. 2011. Tenofovir renal proximal tubular toxicity is regulated by OAT1 and MRP4 transporters. Lab. Invest. 91:852-858.
31. German P, Warren D, West S, Hui J, Kearney BP. 2010. Pharmacokinetics and bioavailability of an integrase and novel pharmacoenhancercontaining single-tablet fixed-dose combination regimen for the treatment of HIV. J. Acquir. Immune Defic. Syndr. 55:323-329.
32. Cohen C, Elion R, Ruane P, Shamblaw D, DeJesus E, Rashbaum B, Chuck SL, Yale K, Liu HC, Warren DR, Ramanathan S, Kearney BP. 2011. Randomized, phase 2 evaluation of two single-tablet regimens elvitegravir/ cobicistat/emtricitabine/ tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for the initial treatment of HIV infection. AIDS 25:F7-F12.