Intracellular Islatravir-Triphosphate in Dried Blood Spots and Peripheral Blood Mononuclear Cells from Pig-Tailed Macaques.

IF 1.5 4区医学 Q4 IMMUNOLOGY

AIDS research and human retroviruses Pub Date : 2024-05-01 Epub Date: 2023-09-12 DOI:10.1089/AID.2023.0059

Vincent Mainella, Mary Morrow, Kristina Brooks, Lane Bushman, Farah Abdelmawla, David Nerguizian, Ye Ji Choi, Dorothy Patton, Yvonne Cosgrove Sweeney, Sravan Kumar Patel, Peter Anderson, Lisa Rohan

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Abstract

The purpose of this study was to evaluate the relationship between intracellular islatravir-triphosphate (ISL-TP) in paired peripheral blood mononuclear cells (PBMCs) and dried blood spots (DBS). Three pig-tailed macaques (PMs) were dosed with a single intravaginal extended-release ISL-etonogestrel film for a period of 31 days. After extraction and quantification, repeated measures correlation (r_rm) was assessed between log-transformed DBS and PBMC ISL-TP concentrations. Twenty-six paired PBMC/DBS samples were included. Peak ISL-TP concentrations in DBS ranged from 262 to 913 fmol/punches, PBMC C_max ranged from 427 to 857 fmol/10⁶ cells. Repeated measures correlation yielded an r_rm value of 0.96 (95% confidence interval 0.92-0.98; p < .0001). Importantly, ISL-TP was quantifiable in DBS and its pharmacokinetics were similar to PBMC in PMs. Human studies should evaluate DBS applications in clinical pharmacokinetic studies to help define ISL's place in the antiretroviral drug armamentarium.

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猪尾猕猴干燥血斑和外周血单核细胞中的细胞内 Islatravir-Triphosphate

本研究旨在评估配对外周血单核细胞（PBMC）和干血斑（DBS）中细胞内异曲韦酯-三磷酸酯（ISL-TP）之间的关系。对三只猪尾猕猴（PMs）进行了为期 31 天的阴道内单次 ISL-etonogestrel 缓释片给药。提取和定量后，评估了经对数变换的 DBS 和 PBMC ISL-TP 浓度之间的重复测量相关性（rrm）。共纳入 26 份成对的 PBMC/DBS 样本。DBS 中 ISL-TP 的峰值浓度范围为 262 至 913 fmol/punches，PBMC Cmax 范围为 427 至 857 fmol/106 cells。重复测量相关性的 rrm 值为 0.96（95% 置信区间为 0.92-0.98; p

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来源期刊

AIDS research and human retroviruses 医学-病毒学

CiteScore

3.10

自引率

6.70%

发文量

201

审稿时长

3-6 weeks

期刊介绍： AIDS Research and Human Retroviruses was the very first AIDS publication in the field over 30 years ago, and today it is still the critical resource advancing research in retroviruses, including AIDS. The Journal provides the broadest coverage from molecular biology to clinical studies and outcomes research, focusing on developments in prevention science, novel therapeutics, and immune-restorative approaches. Cutting-edge papers on the latest progress and research advances through clinical trials and examination of targeted antiretroviral agents lead to improvements in translational medicine for optimal treatment outcomes. AIDS Research and Human Retroviruses coverage includes: HIV cure research HIV prevention science - Vaccine research - Systemic and Topical PreP Molecular and cell biology of HIV and SIV Developments in HIV pathogenesis and comorbidities Molecular biology, immunology, and epidemiology of HTLV Pharmacology of HIV therapy Social and behavioral science Rapid publication of emerging sequence information.