Intracellular Islatravir-Triphosphate in Dried Blood Spots and Peripheral Blood Mononuclear Cells from Pig-Tailed Macaques
Year: 2023
Type: article
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/10 6 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.
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Long Acting Film Technology for Contraception and HIV Prevention (LATCH), Long Acting Film Technology for Contraception and HIV Prevention (LATCH), Training Program for Antiretroviral Discovery, Evaluation and Application Research (ADEAR), Washington National Primate Research Center, WaNPRC Macaca nemestrina SPF Breeding Colony
OpenAlex ID: W4382501445