2025/02/28 by Farhad Ravandi, Sravanti Rangaraju, Hagop M. Kantarjian +12 · 1 voice · 3 citations
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Acute promyelocytic leukemia #Adverse effect #Arsenic #Arsenic trioxide #Chemistry #Cmax #Drug Transport and Resistance Mechanisms #Drug-Induced Ocular Toxicity #Medicine #Oral administration #Pharmacokinetics #Pharmacology #Retinoic acid #Retinoids in leukemia and cellular processes #Tolerability
paper · pdf · doi:10.1182/bloodadvances.2024015453
published in Blood Advances 9(9), 2136-2143 (Elsevier BV)
openalex publication_date 2025/02/28 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/31
ABSTRACT: SY-2101 is a novel oral formulation of arsenic trioxide (ATO). Although IV ATO in combination with all trans retinoic acid is highly efficacious in treating acute promyelocytic leukemia (APL), there remains a significant unmet need due to the treatment burden associated with receiving daily ATO infusions for nearly a year and the risk of complications associated with indwelling central catheters. The pharmacokinetics (PK), safety, and tolerability of SY-2101 and ATO IV after single- and multiple-dose administration and the impact of food on PK for SY-2101 were evaluated in this phase 1 study in 15 participants with APL. SY-2101 in the fasted state demonstrated comparable systemic exposure to ATO IV based on the active metabolite arsenious acid [As(III)], with geometric mean ratios (GMRs) of SY-2101 to ATO IV of 1.00 for area under the plasma concentration (AUC) from 0 hour to last time point (AUC0-last) and from 0 hour to infinity (AUC0-inf). The GMR of SY-2101 to ATO IV maximum concentration (Cmax) was 0.76, as was expected due to the different routes of administration. Comparisons of SY-2101 in fed to fasted states demonstrated similar exposure with GMRs of AUC0-last, AUC0-inf, and Cmax at 1.08, 1.12, and 0.85, respectively, allowing for SY-2101 administration with or without food. SY-2101 was well tolerated. Most adverse events were of low grade. This study provides the first intrapatient PK crossover results directly comparing SY-2101 with ATO IV and supports the likelihood of clinical equivalence between the 2 formulations. This trial was registered at www.ClinicalTrials.gov as #NCT04996030.