ArticleEuropean journal of drug metabolism and pharmacokinetics2021
Population Pharmacokinetic Analysis from First-in-Human Data for HDAC Inhibitor, REC-2282 (AR-42), in Patients with Solid Tumors and Hematologic Malignancies: A Case Study for Evaluating Flat vs. Body Size Normalized Dosing.
Article in European journal of drug metabolism and pharmacokinetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase I Study of AR-42 in Relapsed Myeloma, Chronic Lymphocytic Leukemia, and Lymphoma
Phase I Study of AR-42 and Decitabine in Acute Myeloid Leukemia
Who cites it
4 citing papers in PubMed, 5 citations in OpenAlex.
- Epigenetic Modulation and Bone Metastasis: Evolving Therapeutic Strategies.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Treatment with TNFα and lipolysis-stimulated lipoprotein receptor (LSR) antibody in the presence of HDAC inhibitors promotes apoptosis in human salivary duct adenocarcinoma.Tissue barriers · 2025Article
- Tumor intrinsic properties dictate Fc receptor expression and cancer cachexia associated increase in checkpoint inhibitor clearance.Frontiers in immunology · 2025Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
BACKGROUND AND
objectivesREC-2282 is a novel histone deacetylase inhibitor that has shown antitumor activity in in vitro and in vivo models of malignancy. The aims of this study were to characterize the population pharmacokinetics of REC-2282 (AR-42) from the first-in-human (NCT01129193) and phase I acute myeloid leukemia trials (NCT01798901) and to evaluate potential sources of variability. Additionally, we sought to understand alternate body size descriptors as sources of inter-individual variability (IIV), which was significant for dose-normalized maximum observed concentration and area under the concentration-time curve (AUC).
methodsDatasets from two clinical trials were combined, and population pharmacokinetic analysis was performed using NONMEM and R softwares; patient demographics were tested as covariates.
resultsA successful population pharmacokinetic model was constructed. The pharmacokinetics of REC-2282 were best described by a two-compartment model with one transit compartment for absorption, first-order elimination and a proportional error model. Fat-free mass (FFM) was retained as a single covariate on clearance (CL), though it explained < 3% of the observed variability on CL. Tumor type and formulation were retained as covariates on lag time, and a majority of variability, attributed to absorption, remained unexplained. Computed tomography (CT)-derived lean body weight estimates were lower than estimated lean body weight and fat-free mass measures in most patients. Analysis of dose-normalized AUC vs. body size descriptors suggests flat dosing is most appropriate for REC-2282.
conclusionsFFM was identified as a significant covariate on CL; however, it explained only a very small portion of the IIV; major factors contributing significantly to REC-2282 pharmacokinetic variability remain unidentified.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.