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

Gabriel M Fox,1 Ad F Roffel,2 Jan Hartstra,2 Linda A Bussian,3 Sjoerd P van Marle2 1Department of Clinical Development, Acacia Pharma Ltd, Cambridge, UK; 2PRA Health Sciences, Groningen, the Netherlands; 3Comedica Ltd, Cambridge, UKCorrespondence: Gabriel M FoxDepartment of Clinical Development, Aca...

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Autores principales:	Fox GM, Roffel AF, Hartstra J, Bussian LA, van Marle SP
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	amisulpride antiemetics metabolism elimination radio-labeled Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/a67dd663b38743ce866a2a52a7bc1a3c
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spelling	oai:doaj.org-article:a67dd663b38743ce866a2a52a7bc1a3c2021-12-02T05:49:52ZMetabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers1179-1438https://doaj.org/article/a67dd663b38743ce866a2a52a7bc1a3c2019-12-01T00:00:00Zhttps://www.dovepress.com/metabolism-and-excretion-of-intravenous-radio-labeled-amisulpride-in-h-peer-reviewed-article-CPAAhttps://doaj.org/toc/1179-1438Gabriel M Fox,1 Ad F Roffel,2 Jan Hartstra,2 Linda A Bussian,3 Sjoerd P van Marle2 1Department of Clinical Development, Acacia Pharma Ltd, Cambridge, UK; 2PRA Health Sciences, Groningen, the Netherlands; 3Comedica Ltd, Cambridge, UKCorrespondence: Gabriel M FoxDepartment of Clinical Development, Acacia Pharma Ltd, The Officers’ Mess, Duxford, Cambridge CB22 4QH, UKTel +44 1223 919760Fax +44 1223 919769Email gabrielfox@acaciapharma.comPurpose: Intravenous amisulpride, a dopamine D2/D3 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.Keywords: amisulpride, antiemetics, metabolism, elimination, radio-labeled  Fox GMRoffel AFHartstra JBussian LAvan Marle SPDove Medical Pressarticleamisulprideantiemeticsmetabolismeliminationradio-labeledTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol Volume 11, Pp 161-169 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	amisulpride antiemetics metabolism elimination radio-labeled Therapeutics. Pharmacology RM1-950
spellingShingle	amisulpride antiemetics metabolism elimination radio-labeled Therapeutics. Pharmacology RM1-950 Fox GM Roffel AF Hartstra J Bussian LA van Marle SP Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers
description	Gabriel M Fox,1 Ad F Roffel,2 Jan Hartstra,2 Linda A Bussian,3 Sjoerd P van Marle2 1Department of Clinical Development, Acacia Pharma Ltd, Cambridge, UK; 2PRA Health Sciences, Groningen, the Netherlands; 3Comedica Ltd, Cambridge, UKCorrespondence: Gabriel M FoxDepartment of Clinical Development, Acacia Pharma Ltd, The Officers’ Mess, Duxford, Cambridge CB22 4QH, UKTel +44 1223 919760Fax +44 1223 919769Email gabrielfox@acaciapharma.comPurpose: Intravenous amisulpride, a dopamine D2/D3 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.Keywords: amisulpride, antiemetics, metabolism, elimination, radio-labeled
format	article
author	Fox GM Roffel AF Hartstra J Bussian LA van Marle SP
author_facet	Fox GM Roffel AF Hartstra J Bussian LA van Marle SP
author_sort	Fox GM
title	Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers
title_short	Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers
title_full	Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers
title_fullStr	Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers
title_full_unstemmed	Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers
title_sort	metabolism and excretion of intravenous, radio-labeled amisulpride in healthy, adult volunteers
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/a67dd663b38743ce866a2a52a7bc1a3c
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Metabolism and Excretion of Intravenous, Radio-Labeled Amisulpride in Healthy, Adult Volunteers

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