alexa Intracellular Concentrations of Non-Nucleoside Reverse Transcriptase Inhibitors and its Potential Role on Apoptosis in Peripheral Blood Mononuclear Cells
ISSN: 1948-5964

Journal of Antivirals & Antiretrovirals
Open Access

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Research Article

Intracellular Concentrations of Non-Nucleoside Reverse Transcriptase Inhibitors and its Potential Role on Apoptosis in Peripheral Blood Mononuclear Cells

Akihiko Saitoh1,3*, Dana Dominguez1, Tristan M. Stani1, Steven Rossi2, Edmund Capparelli2 and Stephen A. Spector1,3

1Division of Infectious Diseases, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA

2Division of Pharmacology and Drug Discovery, Department of Pediatrics, University of California San Diego, La Jolla, CA, USA

3Rady Chidlren's Hospital San Diego, CA, USA

*Corresponding Author:
Dr. Akihiko Saitoh, MD
Division of Infectious Diseases
Department of Pediatrics, University of Californi
San Diego, 9500 Gilman Drive, La Jolla
CA 92093-0672, USA
Tel: +1-858-534-7258
Fax: +1-858-534-7411
E-mail: [email protected]

Accepted Date: April 18, 2011; Published Date: April 23, 2011

Citation: Saitoh A, Dominguez D, Stani TM, Rossi S, Capparelli E, et al. (2011) Intracellular Concentrations of Non-Nucleoside Reverse Transcriptase Inhibitors and its Potential Role on Apoptosis in Peripheral Blood Mononuclear Cells. J Antivir Antiretrovir 3: 014-019. doi: 10.4172/jaa.1000029

Copyright: © 2011 Saitoh A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Efavirenz (EFV) and nevirapine (NVP) are non-nucleoside reverse transcriptase inhibitors (NNRTIs) that are frequently used in combination with other antiretrovirals for the treatment of HIV-infected persons. Little information is available regarding the intracellular concentrations (ICs) of EFV and NVP in peripheral blood mononuclear cells (PBMCs) and its potential role for cellular toxicity. Methods: PBMCs from healthy adult donors were treated with or without the mean peak steady-state levels (Cmax) of EFV (12.4µM) and NVP (17.0µM) in human plasma during antiretroviral therapy multiplied by 0.5, 1.0, 2.0 and 4.0. After 48 hr treatment, ICs of EFV and NVP were measured using liquid chromatoagraphy-ion trap/mass spectrometry. The degree of apoptotic cells and mitochondrial membrane potential in PBMCs were measured by flow cytometry. Results: The mean log ICs of x1.0 Cmax NVP in PBMCs (2.00 ± 0.23 µM) were significantly lower than the one of x1.0 Cmax EFV (2.95 ± 0.22 µM) (P < 0.01). Similar significant differences of mean log ICs were observed when the concentration of NNRTIs were x0.5 Cmax (1.62 ± 0.26 µM vs. 2.87 ± 0.13 µM, P < 0.01) and x2.0 Cmax (1.99 ± 0.39 µM vs. 3.11 ± 0.21 µM, P < 0.01). Furthermore, apoptotic PBMCs were lower than PBMC treated with the concentrations of NVP above the plasma Cmax observed clinically in patients as compared to those treated with comparable concentrations of EFV (P < 0.01). Conclusion: These in vitro data suggest that ICs of NVP in PBMCs are significantly lower than ICs of EFV in PBMC and are also associated with less apoptotic PBMCs. The clinical relevance of this observation remains to be elucidated.

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