Intracellular Tenofovir and Emtricitabine Anabolites in Genital, Rectal, and Blood Compartments from First Dose to Steady State
| Autor: | Lane R. Bushman, Brandon Klein, Caitlin Rower, Joseph E. Rower, L. Anthony Guida, Jennifer J. Kiser, Edward M. Gardner, Brent E. Palmer, Samantha MaWhinney, Gregory L. Austin, Jia-Hua Zheng, Carolyn Clayton, Xinhui Chen, Sharon M Seifert, Peter L. Anderson, Amie L. Meditz, Jose R Castillo-Mancilla, Becky Jo Kerr, Julie A. Predhomme |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine medicine.medical_specialty Time Factors Efavirenz Adolescent Anti-HIV Agents Lymphocyte 030106 microbiology Immunology Pharmacology Emtricitabine Peripheral blood mononuclear cell Gastroenterology Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Pharmacokinetics Virology Internal medicine medicine Humans Sex organ Genitalia Prospective Studies 030212 general & internal medicine Tenofovir PReP business.industry Rectum virus diseases Epithelial Cells Middle Aged Spermatozoa Confidence interval Infectious Diseases medicine.anatomical_structure chemistry Leukocytes Mononuclear Female business Intracellular medicine.drug |
| Zdroj: | AIDS Research and Human Retroviruses. 32:981-991 |
| ISSN: | 1931-8405 0889-2229 |
| DOI: | 10.1089/aid.2016.0008 |
| Popis: | The pharmacokinetics (PK) of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP), the active anabolites of tenofovir disoproxil fumarate (TDF), and emtricitabine (FTC) in blood, genital, and rectal compartments was determined in HIV-positive and seronegative adults who undertook a 60-day intensive PK study of daily TDF/FTC (plus efavirenz in HIV positives). Lymphocyte cell sorting, genital, and rectal sampling occurred once per subject, at staggered visits. Among 19 HIV-positive (3 female) and 21 seronegative (10 female) adults, TFV-DP in peripheral blood mononuclear cells (PBMC) accumulated 8.6-fold [95% confidence interval (CI): 7.2–10] from first-dose to steady-state concentration (Css) versus 1.7-fold (95% CI: 1.5–1.9) for FTC-TP. Css was reached in ∼11 and 3 days, respectively. Css values were similar between HIV-negative and HIV-positive individuals. Css TFV-DP in rectal mononuclear cells (1,450 fmol/106 cells, 898–2,340) was achieved in 5 days and was >10 times higher than PBMC (95 fmol/106 cells, 85–106), seminal cells (22 fmol/106 cells, 6–79), and cervical cells (111 fmol/106 cells, 64–194). FTC-TP Css was highest in PBMC (5.7 pmol/106 cells, 5.2–6.1) and cervical cells (7 pmol/106 cells, 2–19) versus rectal (0.8 pmol/106 cells, 0.6–1.1) and seminal cells (0.3 pmol/106 cells, 0.2–0.5). Genital drug concentrations on days 1–7 overlapped with estimated Css, but accumulation characteristics were based on limited data. TFV-DP and FTC-TP in cell sorted samples were highest and achieved most rapidly in CD14+ compared with CD4+, CD8+, and CD19+ cells. Together, these findings demonstrate cell-type and tissue-dependent cellular pharmacology, preferential accumulation of TFV-DP in rectal mononuclear cells, and rapid distribution into rectal and genital compartments. |
| Databáze: | OpenAIRE |
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