Pharmacokinetics and metabolism of [(14)C]-tozadenant (SYN-115), a novel A2a receptor antagonist ligand, in healthy volunteers.

Article Details

Citation
Copy to clipboard

Mancel V, Mathy FX, Boulanger P, English S, Croft M, Kenney C, Knott T, Stockis A, Bani M

Pharmacokinetics and metabolism of [(14)C]-tozadenant (SYN-115), a novel A2a receptor antagonist ligand, in healthy volunteers.

Xenobiotica. 2017 Aug;47(8):705-718. doi: 10.1080/00498254.2016.1221164. Epub 2016 Sep 2.

PubMed ID
27489076 [ View in PubMed
]
Abstract

1. This phase-I study (NCT02240290) was designed to investigate the human absorption, disposition and mass balance of (14)C-tozadenant, a novel A2a receptor antagonist in clinical development for Parkinson s disease. 2. Six healthy male subjects received a single oral dose of tozadenant (240 mg containing 81.47 KBq of [(14)C]-tozadenant). Blood, urine and feces were collected over 14 days. Radioactivity was determined by liquid scintillation counting or accelerator mass spectrometry (AMS). Tozadenant and metabolites were characterized using HPLC-MS/MS and HPLC-AMS with fraction collection. 3. At 4 h, the Cmax of tozadenant was 1.74 mug/mL and AUC(0-t) 35.0 h mug/mL, t1/2 15 h, Vz/F 1.82 L/kg and CL/F 1.40 mL/min/kg. For total [(14)C] radioactivity, the Cmax was 2.29 mug eq/mL at 5 h post-dose and AUC(0-t) 43.9 h mug eq/mL. Unchanged tozadenant amounted to 93% of the radiocarbon AUC(0-48h). At 312 h post-dose, cumulative urinary and fecal excretion of radiocarbon reached 30.5% and 55.1% of the dose, respectively. Unchanged tozadenant reached 11% in urine and 12% of the dose in feces. Tozadenant was excreted as metabolites, including di-and mono-hydroxylated metabolites, N/O dealkylated metabolites, hydrated metabolites. 4. The only identified species circulating in plasma was unchanged tozadenant. Tozadenant was primarily excreted in urine and feces in the form of metabolites.

DrugBank Data that Cites this Article

Drugs