TY  - JOUR
AU  - Jayachandran, Priya
AU  - Garcia-Cremades, Maria
AU  - Vučićević, Katarina
AU  - Bumpus, Namandjé
AU  - Anton, Peter
AU  - Hendrix, Craig
AU  - Savić, Radojka
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3785
AB  - Defining tissue and plasma-specific prophylactic drug concentrations is central to pre-exposure prophylaxis product development for sexual transmission of HIV-1. Pharmacokinetic (PK) data from study RMP-02/MTN-006 comparing single dose oral tenofovir disoproxil fumarate with single and multiple dose rectal tenofovir (TFV) gel administration in HIV-1 seronegative adults was used to construct a multicompartment plasma-rectal tissue population PK model for TFV and tenofovir-diphosphate (TFVdp) in plasma and rectal tissue. PK data were collected in five matrices: TFV (plasma, rectal tissue homogenate), TFVdp (peripheral blood mononuclear cells, rectal mononuclear cells (MMCs), rectal tissue homogenate). A viral growth compartment and a delayed effect compartment for p24 antigen expression measured from an ex vivo explant assay described HIV-1 infection and replication. Using a linear PK/pharmacodynamic model, MMC TFVdp levels over 9,000 fmol/million cells in the explant assay provided apparent viral replication suppression down to 1%. Parameters were estimated using NONMEM version 7.4.
PB  - American Society for Clinical Pharmacology and Therapeutics
T2  - CPT: Pharmacometrics and Systems Pharmacology
T1  - A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention
VL  - 10
SP  - 179
EP  - 187
DO  - 10.1002/psp4.12583
ER  - 

@article{
author = "Jayachandran, Priya and Garcia-Cremades, Maria and Vučićević, Katarina and Bumpus, Namandjé and Anton, Peter and Hendrix, Craig and Savić, Radojka",
year = "2021",
abstract = "Defining tissue and plasma-specific prophylactic drug concentrations is central to pre-exposure prophylaxis product development for sexual transmission of HIV-1. Pharmacokinetic (PK) data from study RMP-02/MTN-006 comparing single dose oral tenofovir disoproxil fumarate with single and multiple dose rectal tenofovir (TFV) gel administration in HIV-1 seronegative adults was used to construct a multicompartment plasma-rectal tissue population PK model for TFV and tenofovir-diphosphate (TFVdp) in plasma and rectal tissue. PK data were collected in five matrices: TFV (plasma, rectal tissue homogenate), TFVdp (peripheral blood mononuclear cells, rectal mononuclear cells (MMCs), rectal tissue homogenate). A viral growth compartment and a delayed effect compartment for p24 antigen expression measured from an ex vivo explant assay described HIV-1 infection and replication. Using a linear PK/pharmacodynamic model, MMC TFVdp levels over 9,000 fmol/million cells in the explant assay provided apparent viral replication suppression down to 1%. Parameters were estimated using NONMEM version 7.4.",
publisher = "American Society for Clinical Pharmacology and Therapeutics",
journal = "CPT: Pharmacometrics and Systems Pharmacology",
title = "A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention",
volume = "10",
pages = "179-187",
doi = "10.1002/psp4.12583"
}

Jayachandran, P., Garcia-Cremades, M., Vučićević, K., Bumpus, N., Anton, P., Hendrix, C.,& Savić, R.. (2021). A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention. in CPT: Pharmacometrics and Systems Pharmacology
American Society for Clinical Pharmacology and Therapeutics., 10, 179-187.
https://doi.org/10.1002/psp4.12583

Jayachandran P, Garcia-Cremades M, Vučićević K, Bumpus N, Anton P, Hendrix C, Savić R. A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention. in CPT: Pharmacometrics and Systems Pharmacology. 2021;10:179-187.
doi:10.1002/psp4.12583 .

Jayachandran, Priya, Garcia-Cremades, Maria, Vučićević, Katarina, Bumpus, Namandjé, Anton, Peter, Hendrix, Craig, Savić, Radojka, "A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention" in CPT: Pharmacometrics and Systems Pharmacology, 10 (2021):179-187,
https://doi.org/10.1002/psp4.12583 . .