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dc.creatorJayachandran, Priya
dc.creatorGarcia-Cremades, Maria
dc.creatorVučićević, Katarina
dc.creatorBumpus, Namandjé
dc.creatorAnton, Peter
dc.creatorHendrix, Craig
dc.creatorSavić, Radojka
dc.date.accessioned2021-02-23T10:01:36Z
dc.date.available2021-02-23T10:01:36Z
dc.date.issued2021
dc.identifier.issn2163-8306
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/3785
dc.description.abstractDefining 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.publisherAmerican Society for Clinical Pharmacology and Therapeutics
dc.relationPre- Clinical/Clinical HIV Topical Microbicide Program (U19 AI AI060614)
dc.relationMicrobicide Trials Network Laboratory Center (UM1 AI106707)
dc.relationBill and Melinda Gates Foundation (Contract ID OPP1099837)
dc.relationJohns Hopkins University Center for AIDS Research (P30 AI042855)
dc.relationP.J. was supported by grant T32 GM007546 from the National Institute of General Medical Sciences (NIGMS).
dc.rightsopenAccess
dc.sourceCPT: Pharmacometrics and Systems Pharmacology
dc.titleA Mechanistic In Vivo/Ex Vivo Pharmacokinetic-Pharmacodynamic Model of Tenofovir for HIV Prevention
dc.typearticle
dc.rights.licenseBY
dcterms.abstractВучићевић, Катарина; Јаyацхандран, Приyа; Гарциа-Цремадес, Мариа; Бумпус, Намандјé; Aнтон, Петер; Хендриx, Цраиг; Савић, Радојка;
dc.citation.volume10
dc.citation.spage179
dc.citation.epage187
dc.identifier.wos000615319000001
dc.identifier.doi10.1002/psp4.12583
dc.identifier.scopus2-s2.0-85100593175
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs/bitstream/id/8972/bitstream_8972.pdf
dc.type.versionpublishedVersion


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