Comparison of Concentration-time Course of Plasma and Intracellular Raltegravir in Healthy Volunteers

Summary

The investigators hypothesize that the concentration-time profile of raltegravir is different in cells than that in plasma. Intracellular raltegravir concentrations may be higher and its half-life longer than in plasma. This may explain the efficacy of raltegravir despite variable plasma concentrations.

Timeline

Start

2009-12

Primary completion

2010-03

Completion

2010-03

Publications

• Background Barry MG, Khoo SH, Veal GJ, Hoggard PG, Gibbons SE, Wilkins EG, Williams O, Breckenridge AM, Back DJ. The effect of zidovudine dose on the formation of intracellular phosphorylated metabolites. AIDS. 1996 Oct;10(12):1361-7. doi: 10.1097/00002030-199610000-00008.
• Background Long MC, Bennetto-Hood C, Acosta EP. A sensitive HPLC-MS-MS method for the determination of raltegravir in human plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 May 15;867(2):165-71. doi: 10.1016/j.jchromb.2008.03.022. Epub 2008 Apr 1.
• Background Ter Heine R, Hillebrand MJ, Rosing H, van Gorp EC, Mulder JW, Beijnen JH, Huitema AD. Quantification of the HIV-integrase inhibitor raltegravir and detection of its main metabolite in human plasma, dried blood spots and peripheral blood mononuclear cell lysate by means of high-performance liquid chromatography tandem mass spectrometry. J Pharm Biomed Anal. 2009 Feb 20;49(2):451-8. doi: 10.1016/j.jpba.2008.11.025. Epub 2008 Nov 27.
• Background Wenning LA, Hanley WD, Brainard DM, Petry AS, Ghosh K, Jin B, Mangin E, Marbury TC, Berg JK, Chodakewitz JA, Stone JA, Gottesdiener KM, Wagner JA, Iwamoto M. Effect of rifampin, a potent inducer of drug-metabolizing enzymes, on the pharmacokinetics of raltegravir. Antimicrob Agents Chemother. 2009 Jul;53(7):2852-6. doi: 10.1128/AAC.01468-08. Epub 2009 May 11.
• Background Wenning, L. A., E. Hwang, et al. (2008). Pharmacokinetic/Pharmacodynamic (PK/PD) Analyses for Raltegravir (RAL) in Phase III Studies in Treatment Experienced HIV- Infected Patients Following 48 Weeks of Treatment. ICAAC. Washington DC, USA
• Background Merck &Co Inc. (2007). Isentress (raltegravir) tablets. FDA approved label.

Drugs

Indications