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

Abstract

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 ¹⁴C-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 ¹⁴C-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 ¹⁴C-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.