Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers

PURPOSE: Intravenous amisulpride, a dopamine D(2)/D(3) antagonist, has recently been shown in trials to be an effective antiemetic at low doses. This study was conducted to investigate the metabolism and elimination of a single dose of intravenous (14)C-labeled amisulpride in healthy, adult volunteers. PATIENTS AND METHODS: Six healthy male volunteers aged 18–65 years were given a single 10 mg dose of (14)C-labeled amisulpride containing not more than 1.8 MBq of radioactivity, infused over 4 mins. Concentrations of amisulpride and total radioactivity were measured in plasma, whole blood, urine and feces at various time points up to 168 hrs after dosing. Metabolites detected in plasma, urine and feces were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS) with in-line radiometric detection. RESULTS: The mean recovery of radioactivity in excreta was 96.4% (range 92.0–98.5%), of which 73.6% (range 70.6–79.2%) was recovered from urine and 22.8% (range 18.9–25.7%) from feces. Four metabolites of amisulpride were detected in urine, representing 15.0% of the excreted dose; three of these were also present in feces, representing 6.1% of the excreted dose. No metabolites were detected in plasma. Excretion was initially rapid, with about two-thirds of the drug-related material eliminated within 12 hrs, primarily in the urine. A second, slower phase of excretion was predominantly fecal and was essentially complete by 96 hrs after dosing. The terminal plasma elimination half-life of parent amisulpride was 3.7 hrs and that of total (14)C-labeled drug material was 4.2 hrs. CONCLUSION: Intravenous amisulpride undergoes limited metabolism and is excreted primarily via the renal route. CLINICAL TRIAL REGISTRY NUMBER: ClinicalTrials.gov NCT02881840.