dc.creator | Jayachandran, Priya | |
dc.creator | Garcia-Cremades, Maria | |
dc.creator | Vučićević, Katarina | |
dc.creator | Bumpus, Namandjé | |
dc.creator | Anton, Peter | |
dc.creator | Hendrix, Craig | |
dc.creator | Savić, Radojka | |
dc.date.accessioned | 2021-02-23T10:01:36Z | |
dc.date.available | 2021-02-23T10:01:36Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 2163-8306 | |
dc.identifier.uri | https://farfar.pharmacy.bg.ac.rs/handle/123456789/3785 | |
dc.description.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. | |
dc.publisher | American Society for Clinical Pharmacology and Therapeutics | |
dc.relation | Pre-
Clinical/Clinical HIV Topical Microbicide Program (U19 AI AI060614) | |
dc.relation | Microbicide Trials Network Laboratory Center (UM1 AI106707) | |
dc.relation | Bill and Melinda Gates Foundation
(Contract ID OPP1099837) | |
dc.relation | Johns Hopkins University Center for AIDS
Research (P30 AI042855) | |
dc.relation | P.J. was supported by grant T32 GM007546 from
the National Institute of General Medical Sciences (NIGMS). | |
dc.rights | openAccess | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | |
dc.source | CPT: Pharmacometrics and Systems Pharmacology | |
dc.title | A Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention | |
dc.type | article | |
dc.rights.license | BY | |
dcterms.abstract | Вучићевић, Катарина; Јаyацхандран, Приyа; Гарциа-Цремадес, Мариа; Бумпус, Намандјé; Aнтон, Петер; Хендриx, Цраиг; Савић, Радојка; | |
dc.citation.volume | 10 | |
dc.citation.spage | 179 | |
dc.citation.epage | 187 | |
dc.citation.rank | M22 | |
dc.identifier.wos | 000615319000001 | |
dc.identifier.doi | 10.1002/psp4.12583 | |
dc.identifier.scopus | 2-s2.0-85100593175 | |
dc.identifier.fulltext | https://farfar.pharmacy.bg.ac.rs/bitstream/id/8972/bitstream_8972.pdf | |
dc.type.version | publishedVersion | |