Plasma and intracellular (peripheral blood mononuclear cells) pharmacokinetics of once-daily raltegravir (800 milligrams) in HIV-infected patients

Antimicrobial Agents and Chemotherapy

Volumn 55, Issue 1, 2011, Pages 72-75

  Moltó, José ^a,c   Valle, Marta ^b,c   Back, David ^d   Cedeño, Samandhy ^a   Watson, Victoria ^d,e   Liptrott, Neill ^d,e   Egan, Deirdre ^d,e   Miranda, Cristina ^a   Barbanoj, Manuel J ^b,c   Clotet, Bonaventura ^a,c  

^a HOSPITAL UNIVERSITARI GERMANS TRIAS I PUJOL   (Spain)

^b HOSPITAL CLÍNIC   (Spain)

^c UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^d UNIVERSITY OF LIVERPOOL   (United Kingdom)

^e ROYAL LIVERPOOL AND BROADGREEN UNIVERSITY HOSPITALS NHS TRUST   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

LOPINAVIR PLUS RITONAVIR; RALTEGRAVIR; VIRUS RNA;

ADULT; AREA UNDER THE CURVE; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG TOLERABILITY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IC 50; LIQUID CHROMATOGRAPHY; MALE; MAXIMUM ALLOWABLE CONCENTRATION; MONOTHERAPY; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; TANDEM MASS SPECTROMETRY;

CELLS, CULTURED; DRUG ADMINISTRATION SCHEDULE; HIV INFECTIONS; HUMANS; LEUKOCYTES, MONONUCLEAR; RITONAVIR;

EID: 78650673812     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00789-10     Document Type: Article

References (22)

1. Benech, H., F. Theodoro, A. Herbet, N. Page, D. Schlemmer, A. Pruvost, J. Grassi, and J. R. Deverre. 2004. Peripheral blood mononuclear cell counting using a DNA-detection-based method. Anal. Biochem. 330:172-174.
2. Croxtall, J. D., K. A. Lyseng-Williamson, and C. M. Perry. 2008. Raltegravir. Drugs 68:131-138.
3. Else, L., V. Watson, J. Tjia, A. Hughes, M. Siccardi, S. Khoo, and D. Back. Validation of a rapid and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) assay for the simultaneous determination of existing and new antiretroviral compounds. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 878:1455-1465.
4. Fayet-Mello, A., T. Buclin, C. Franc, S. Colombo, S. Cruchon, N. Guignard, J. Biollaz, A. Telenti, L. Decosterd, and M. Cavassini. 2010. Intracellular and plasma pharmacokinetics of raltegravir in HIV-infected patients, abstr. 614. Abstr. 17th Conf. Retrovir. Opportunistic Infect.
5. Grinsztejn, B., B. Y. Nguyen, C. Katlama, J. M. Gatell, A. Lazzarin, D. Vittecoq, C. J. Gonzalez, J. Chen, C. M. Harvey, and R. D. Isaacs. 2007. 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 369:1261-1269.
6. Hazuda, D. J., P. Felock, M. Witmer, A. Wolfe, K. Stillmock, J. A. Grobler, A. Espeseth, L. Gabryelski, W. Schleif, C. Blau, and M. D. Miller. 2000. Inhibitors of strand transfer that prevent integration and inhibit HIV-1 replication in cells. Science 287:646-650.
7. Hicks, C., and R. M. Gulick. 2009. Raltegravir: the first HIV type 1 integrase inhibitor. Clin. Infect. Dis. 48:931-939.
8. Iwamoto, M., L. A. Wenning, A. S. Petry, M. Laethem, M. De Smet, J. T. Kost, S. A. Merschman, K. M. Strohmaier, S. Ramael, K. C. Lasseter, J. A. Stone, K. M. Gottesdiener, and J. A. Wagner. 2008. Safety, tolerability, and pharmacokinetics of raltegravir after single and multiple doses in healthy subjects. Clin. Pharmacol. Ther. 83:293-299.
9. Lennox, J. L., E. Dejesus, D. S. Berger, A. Lazzarin, R. B. Pollard, J. V. Ramalho Madruga, J. Zhao, H. Wan, C. L. Gilbert, H. Teppler, A. J. Rodgers, R. J. Barnard, M. D. Miller, M. J. Dinubile, B. Y. Nguyen, R. Leavitt, and P. Sklar. 2010. Raltegravir versus efavirenz regimens in treatment-naïve HIV-1-infected Patients: 96-week efficacy, durability, subgroup, safety, and metabolic analyses. J. Acquir. Immune Defic. Syndr. 55:39-48.
10. Markowitz, M., J. O. Morales-Ramirez, B. Y. Nguyen, C. M. Kovacs, R. T. Steigbigel, D. A. Cooper, R. Liporace, R. Schwartz, R. Isaacs, L. R. Gilde, L. Wenning, J. Zhao, and H. Teppler. 2006. 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. 43:509-515.
11. Markowitz, M., B. Y. Nguyen, E. Gotuzzo, F. Mendo, W. Ratanasuwan, C. Kovacs, G. Prada, J. O. Morales-Ramirez, C. S. Crumpacker, R. D. Isaacs, H. Campbell, K. M. Strohmaier, H. Wan, R. M. Danovich, and H. Teppler. 2009. Sustained antiretroviral effect of raltegravir after 96 weeks of combination therapy in treatment-naive patients with HIV-1 infection. J. Acquir. Immune Defic. Syndr. 52:350-356.
12. Markowitz, M., B. Y. Nguyen, E. Gotuzzo, F. Mendo, W. Ratanasuwan, C. Kovacs, G. Prada, J. O. Morales-Ramirez, C. S. Crumpacker, R. D. Isaacs, L. R. Gilde, H. Wan, M. D. Miller, L. A. Wenning, and H. Teppler. 2007. Rapid and durable antiretroviral effect of the HIV-1 integrase inhibitor raltegravir as part of combination therapy in treatment-naive patients with HIV-1 infection: results of a 48-week controlled study. J. Acquir. Immune Defic. Syndr. 46:125-133.
13. Miller, M., et al. 2008. Analysis of resistance to the HIV-1 integrase inhibitor raltegravir: results from the Benchmark 1 and 2, abstr. H-898. Abstr. 48th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
14. Moss, D., W. S. Kwan, N. Liptrott, M. Siccardi, D. Anstee, S. Khoo, D. Back, and A. Owen. 2010. Raltegravir is a substrate for the influx transporters OAT1 and PEPT1 and the efflux transporter Pgp but it is not transported by OATP1A2, OATP1B1, OATP1B3, OCT1, NTCO, or PEPT2, abstr. 613. Abstr. 17th Conf. Retrovir. Opportunistic Infect.
15. Murray, J. M., S. Emery, A. D. Kelleher, M. Law, J. Chen, D. J. Hazuda, B. Y. Nguyen, H. Teppler, and D. A. Cooper. 2007. Antiretroviral therapy with the integrase inhibitor raltegravir alters decay kinetics of HIV, significantly reducing the second phase. AIDS 21:2315-2321.
16. Nilsson, C., S. Aboud, K. Karlen, B. Hejdeman, W. Urassa, and G. Biberfeld. 2008. Optimal blood mononuclear cell isolation procedures for gamma interferon enzyme-linked immunospot testing of healthy Swedish and Tanzanian subjects. Clin. Vaccine Immunol. 15:585-589.
17. Panel on Antiretroviral Guidelines for Adults and Adolescents. 2009. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. U.S. Department of Health and Human Services, Washington, DC. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf.
18. Poirier, J. M., P. Robidou, and P. Jaillon. 2008. Quantification of the HIVintegrase inhibitor raltegravir (MK-0518) in human plasma by high-performance liquid chromatography with fluorescence detection. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 867:277-281.
19. Ruitenberg, J. J., C. B. Mulder, V. C. Maino, A. L. Landay, and S. A. Ghanekar. 2006. VACUTAINER CPT and Ficoll density gradient separation perform equivalently in maintaining the quality and function of PBMC from HIV seropositive blood samples. BMC Immunol. 7:11.
20. Steigbigel, R. T., D. A. Cooper, P. N. Kumar, J. E. Eron, M. Schechter, M. Markowitz, M. R. Loutfy, J. L. Lennox, J. M. Gatell, J. K. Rockstroh, C. Katlama, P. Yeni, A. Lazzarin, B. Clotet, J. Zhao, J. Chen, D. M. Ryan, R. R. Rhodes, J. A. Killar, L. R. Gilde, K. M. Strohmaier, A. R. Meibohm, M. D. Miller, D. J. Hazuda, M. L. Nessly, M. J. DiNubile, R. D. Isaacs, B. Y. Nguyen, and H. Teppler. 2008. Raltegravir with optimized background therapy for resistant HIV-1 infection. N. Engl. J. Med. 359:339-354.
21. Summa, V., A. Petrocchi, F. Bonelli, B. Crescenzi, M. Donghi, M. Ferrara, F. Fiore, C. Gardelli, O. Gonzalez Paz, D. J. Hazuda, P. Jones, O. Kinzel, R. Laufer, E. Monteagudo, E. Muraglia, E. Nizi, F. Orvieto, P. Pace, G. Pescatore, R. Scarpelli, K. Stillmock, M. V. Witmer, and M. Rowley. 2008. Discovery of raltegravir, a potent, selective orally bioavailable HIV-integrase inhibitor for the treatment of HIV-AIDS infection. J. Med. Chem. 51:5843-5855.
22. ter Heine, R., J. W. Mulder, E. C. M. van Gorp, J. F. P. Wagenaar, J. H. Beijnen, and A. D. R. Huitema. 2010. Intracellular and plasma steady-state pharmacokinetics of raltegravir, darunavir, etravirine and ritonavir in heavily pre-treated HIV-infected patients Br. J. Clin. Pharmacol. 69:475-483.