Model Linking Plasma and Intracellular Tenofovir/Emtricitabine with Deoxynucleoside Triphosphates

• Published in: PloS one Vol. 11; no. 11; p. e0165505
• Main Authors: Chen, Xinhui, Seifert, Sharon M., Castillo-Mancilla, Jose R., Bushman, Lane R., Zheng, Jia-Hua, Kiser, Jennifer J., MaWhinney, Samantha, Anderson, Peter L.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 10.11.2016; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; Adult; AIDS; Analogs; Analysis; Anti-HIV Agents - blood; Anti-HIV Agents - metabolism; Anti-HIV Agents - pharmacokinetics; Anti-HIV Agents - pharmacology; Antiretroviral agents; Antiretroviral drugs; Biology and Life Sciences; Computer Simulation; Data processing; Deoxyadenine Nucleotides - metabolism; Deoxyadenosine; Deoxycytosine Nucleotides - metabolism; Diphosphates - metabolism; Disease prevention; DNA polymerases; Dosage; Drug dosages; Emtricitabine; Emtricitabine - blood; Emtricitabine - metabolism; Emtricitabine - pharmacokinetics; Emtricitabine - pharmacology; Female; Health aspects; HIV; HIV - drug effects; HIV Infections - drug therapy; Human immunodeficiency virus; Humans; Infections; Intracellular; Lentivirus; Leukocytes (mononuclear); Male; Medicine and Health Sciences; Metabolism; Metabolites; Middle Aged; Models, Biological; Nonlinear analysis; Peripheral blood mononuclear cells; Pharmaceutical sciences; Pharmacodynamics; Pharmacokinetics; Pharmacology; Pharmacy; Plasma; Polyphosphates - metabolism; Prophylaxis; Prospective Studies; Research and Analysis Methods; Retroviridae; RNA-directed DNA polymerase; Simulation; Tenofovir; Tenofovir - blood; Tenofovir - metabolism; Tenofovir - pharmacokinetics; Tenofovir - pharmacology; Young Adult; United States > US; Colorado

The coformulation of the nucleos(t)ide analogs (NA) tenofovir (TFV) disoproxil fumarate (TDF) and emtricitabine (FTC) is approved for HIV-infection treatment and prevention. Plasma TFV and FTC undergo complicated hybrid processes to form, accumulate, and retain as their active intracellular anabolit...