Darunavir is predominantly unbound to protein in cerebrospinal fluid and concentrations exceed the wild-type HIV-1 median 90% inhibitory concentration

Journal of Antimicrobial Chemotherapy

Volumn 68, Issue 3, 2013, Pages 684-689

  Croteau, David ^a   Rossi, Steven S ^b   Best, Brookie M ^b,c   Capparelli, Edmund ^b   Ellis, Ronald J ^a   Clifford, David B ^d   Collier, Ann C ^e   Gelman, Benjamin B ^f   Marra, Christina M ^e   Mcarthur, Justin ^g   Mccutchan, J Allen ^h   Morgello, Susan ⁱ   Simpson, David M ⁱ   Grant, Igor ^j   Letendre, Scott ^h  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e UNIVERSITY OF WASHINGTON   (United States)

^f University of Texas Medical Branch School of Medicine   (United States)

^g JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

ⁱ MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^j UNIVERSITY OF CALIFORNIA   (United States)

more..

Author keywords

Antiretroviral therapy; Central nervous system; HIV; Protein binding

Indexed keywords

DARUNAVIR; RITONAVIR; VIRUS RNA;

ADULT; ARTICLE; CLINICAL ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG PROTEIN BINDING; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IN VITRO STUDY; LIQUID CHROMATOGRAPHY; OBSERVATIONAL STUDY; PROTEIN CEREBROSPINAL FLUID LEVEL; TANDEM MASS SPECTROMETRY;

ANTI-HIV AGENTS; CEREBROSPINAL FLUID; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CHROMATOGRAPHY, LIQUID; FEMALE; HIV INFECTIONS; HUMANS; MALE; MIDDLE AGED; PLASMA; PROTEIN BINDING; PROTEINS; SPECIMEN HANDLING; SULFONAMIDES; TANDEM MASS SPECTROMETRY; ULTRAFILTRATION;

EID: 84873600385     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dks441     Document Type: Article

References (30)

1. Heaton RK, Franklin DR, Ellis RJ et al. HIV-associated neurocognitive disorders before and during the era of combination antiretroviral therapy: differences in rates, nature, and predictors. J Neurovirol 2011; 17: 3-16.
2. Ellis RJ, Hsia K, Spector SA et al. Cerebrospinal fluid human immunodeficiency virus type 1 RNA levels are elevated in neurocognitively impaired individuals with acquired immunodeficiency syndrome. HIV Neurobehavioral Research Center Group. Ann Neurol 1997; 42: 679-88.
3. Ellis RJ, Moore DJ, Childers ME et al. Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA. Arch Neurol 2002; 59: 923-8.
4. McArthur JC, McClernon DR, Cronin MF et al. Relationship between human immunodeficiency virus-associated dementia and viral load in cerebrospinal fluid and brain. Ann Neurol 1997; 42: 689-98.
5. Sevigny JJ, Albert SM, McDermott MP et al. Evaluation of HIV RNA and markers of immune activation as predictors of HIV-associated dementia. Neurology 2004; 63: 2084-90.
6. Letendre SL, Marquie-Beck J, Capparelli E et al. Validation of the CNS penetration-effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol 2008; 65: 65-70.
7. Marra CM, Zhao Y, Clifford DB et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS 2009; 23: 1359-66.
8. Cysique LA, Vaida F, Letendre S et al. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology 2009; 73: 342-8.
9. Letendre SL, McCutchan JA, Childers ME et al. Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol 2004; 56: 416-23.
10. Tozzi V, Balestra P, Salvatori MF et al. Changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. J Acquir Immune Defic Syndr 2009; 52: 56-63.
11. Kis O, Robillard K, Chan GNY et al. The complexities of antiretroviral drug-drug interactions: role of ABC and SLC transporters. Trends Pharmacol Sci 2009; 31: 22-35.
12. Dow N. Determination of compound binding to plasma proteins. In: Enna SJ, Williams M, eds. Current Protocols in Pharmacology. Wiley Online Library, 2006; 7.5.1-15.
13. Koh Y, Hirotomo N, Kenji M et al. Novel bis-tetrahydrofuranylurethane-containing nonpeptidic protease inhibitor (PI) UIC-94017 (TMC114) with potent activity against multi-PI-resistant human immunodeficiency virus in vitro. Antimicrob Agents Chem 2003; 47: 3123-9.
14. Ghosh AK, Chapsal BD, Weber IT et al. Design of HIV protease inhibitors targeting protein backbone: an effective strategy for combating drug resistance. Acc Chem Res 2008; 41: 78-86.
15. Rittweger M, Arasteh K. Clinical pharmacokinetics of darunavir. Clin Pharmacokinet 2007; 46: 739-56.
16. Adam P, Sobek O, Taborsky L et al. CSF and serum orosomucoid (a-1-acid glycoprotein) in patients with multiple sclerosis: a comparison among particular subgroups of MS patients. Clin Chim Acta 2003; 334: 107-10.
17. Abbott NJ, Patabendige AA, Dolman DE et al. Structure and function of the blood-brain barrier. Neurobiol Dis 2010; 37: 13-25.
18. Haas DW, Johnson B, Nicotera J et al. Effects of ritonavir on indinavir pharmacokinetics in cerebrospinal fluid and plasma. Antimicrob Agents Chemother 2003; 47: 2131-7.
19. Best BM, Letendre SL, Brigid E et al. Low atazanavir concentrations in cerebrospinal fluid. AIDS 2009; 23: 83-7.
20. Capparelli EV, Holland D, Okamoto C et al. Lopinavir concentrations in cerebrospinal fluid exceed the 50% inhibitory concentration for HIV. AIDS 2005; 19: 949-52.
21. Letendre SL, Capparelli EV, Ellis RJ et al. Indinavir population pharmacokinetics in plasma and cerebrospinal fluid. The HIV Neurobehavioral Research Center Group. Antimicrob Agents Chemother 2000; 44: 2173-5.
22. Bachmeier CJ, Spitzenberger TJ, Elmquist WF et al. Quantitative assessment of HIV-1 protease inhibitor interactions with drug efflux transporters in the blood-brain barrier. Pharm Res 2005; 22: 1259-68.
23. Varatharajan L, Thomas SA. The transport of anti-HIV drugs across blood-CNS interfaces: summary of current knowledge and recommendations for further research. Antiviral Res 2009; 82: A99-109.
24. Croteau D, Letendre S, Best BM et al. Therapeutic amprenavir concentrations in cerebrospinal fluid. Antimicrob Agents Chemother 2012; 56: 1985-9.
25. Ellis RJ, Gamst AC, Capparelli E et al. Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 2000; 54: 927-36.
26. Wiley C, Schrier R, Nelson J et al. Cellular localization of human immunodeficiency virus infection within the brains of acquired immune deficiency syndrome patients. Proc Natl Acad Sci USA 1986; 83: 7089-93.
27. Back D, Sekar V, Hoetelmans RM. Darunavir: pharmacokinetics and drug interactions. Antivir Ther 2008; 13: 1-13.
28. Boffito M, Jackson A, Amara A et al. Pharmacokinetics of once-daily darunavir-ritonavir and atazanavir-ritonavir over 72 hours following drug cessation. Antimicrob Agents Chemother 2011; 55: 4218-23.
29. Yilmaz A, Izadkhashti A, Price RW et al. Darunavir concentrations in cerebrospinal fluid and blood in HIV-1-infected individuals. AIDS Res Hum Retroviruses 2009; 25: 457-61.
30. Calcagno A, Yilmaz A, Cusato J et al. Determinants of darunavir cerebrospinal fluid concentrations: impact of once daily dosing and pharmacogenetics. AIDS 2012; 26: 1529-33.