Cargando…

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans

This study aimed to explore pharmacokinetics, pharmacodynamics, and safety/tolerability of MT921, an injectable cholic acid, after a single subcutaneous administration to healthy volunteers. A randomized, double-blinded, placebo-controlled, single dose-ascending phase 1 study enrolled 24 subjects wh...

Descripción completa

Detalles Bibliográficos
Autores principales: Chung, Hyewon, Park, Jin-Woo, Kim, Dai-Hyun, Seo, Soo-Hong, Kim, Kyoung-Ah, Lee, Woo-Shun, Park, Ji-Young
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400465/
https://www.ncbi.nlm.nih.gov/pubmed/34451926
http://dx.doi.org/10.3390/ph14080830
_version_ 1783745321253208064
author Chung, Hyewon
Park, Jin-Woo
Kim, Dai-Hyun
Seo, Soo-Hong
Kim, Kyoung-Ah
Lee, Woo-Shun
Park, Ji-Young
author_facet Chung, Hyewon
Park, Jin-Woo
Kim, Dai-Hyun
Seo, Soo-Hong
Kim, Kyoung-Ah
Lee, Woo-Shun
Park, Ji-Young
author_sort Chung, Hyewon
collection PubMed
description This study aimed to explore pharmacokinetics, pharmacodynamics, and safety/tolerability of MT921, an injectable cholic acid, after a single subcutaneous administration to healthy volunteers. A randomized, double-blinded, placebo-controlled, single dose-ascending phase 1 study enrolled 24 subjects who were assigned to three groups (60 mg, 120 mg, and 150 mg) of MT921. Blood samples were obtained for a 24-h period before and after injecting MT921 to the submental fat area. Plasma concentrations of cholic acid and deoxycholic acid were determined for pharmacokinetic analysis. Levels of free fatty acid, triglyceride, and total cholesterol were measured for pharmacodynamic analysis. Safety and tolerability were assessed until 21 days post-dose. While systemic exposure to cholic acid tended to increase as the MT921 dose increased, pharmacokinetic profiles of deoxycholic acid were similar among dose groups without showing significant changes. Pharmacodynamic profiles were comparable when measured at baseline and post-dose. The most frequent adverse events were injection site pain and edema. All adverse drug reactions resolved without treatment. MT921 appeared to be well-tolerated after an injection to the submental area at a dose up to 150 mg. Systemic exposure to cholic acid increased as the dose increased. Blood lipid profiles and deoxycholic acid levels were not affected by MT921 treatment.
format Online
Article
Text
id pubmed-8400465
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84004652021-08-29 Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans Chung, Hyewon Park, Jin-Woo Kim, Dai-Hyun Seo, Soo-Hong Kim, Kyoung-Ah Lee, Woo-Shun Park, Ji-Young Pharmaceuticals (Basel) Article This study aimed to explore pharmacokinetics, pharmacodynamics, and safety/tolerability of MT921, an injectable cholic acid, after a single subcutaneous administration to healthy volunteers. A randomized, double-blinded, placebo-controlled, single dose-ascending phase 1 study enrolled 24 subjects who were assigned to three groups (60 mg, 120 mg, and 150 mg) of MT921. Blood samples were obtained for a 24-h period before and after injecting MT921 to the submental fat area. Plasma concentrations of cholic acid and deoxycholic acid were determined for pharmacokinetic analysis. Levels of free fatty acid, triglyceride, and total cholesterol were measured for pharmacodynamic analysis. Safety and tolerability were assessed until 21 days post-dose. While systemic exposure to cholic acid tended to increase as the MT921 dose increased, pharmacokinetic profiles of deoxycholic acid were similar among dose groups without showing significant changes. Pharmacodynamic profiles were comparable when measured at baseline and post-dose. The most frequent adverse events were injection site pain and edema. All adverse drug reactions resolved without treatment. MT921 appeared to be well-tolerated after an injection to the submental area at a dose up to 150 mg. Systemic exposure to cholic acid increased as the dose increased. Blood lipid profiles and deoxycholic acid levels were not affected by MT921 treatment. MDPI 2021-08-23 /pmc/articles/PMC8400465/ /pubmed/34451926 http://dx.doi.org/10.3390/ph14080830 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chung, Hyewon
Park, Jin-Woo
Kim, Dai-Hyun
Seo, Soo-Hong
Kim, Kyoung-Ah
Lee, Woo-Shun
Park, Ji-Young
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans
title Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans
title_full Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans
title_fullStr Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans
title_full_unstemmed Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans
title_short Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Cholic Acid (MT921) after a Subcutaneous Injection in the Submental Area to Humans
title_sort safety, tolerability, pharmacokinetics, and pharmacodynamics of cholic acid (mt921) after a subcutaneous injection in the submental area to humans
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400465/
https://www.ncbi.nlm.nih.gov/pubmed/34451926
http://dx.doi.org/10.3390/ph14080830
work_keys_str_mv AT chunghyewon safetytolerabilitypharmacokineticsandpharmacodynamicsofcholicacidmt921afterasubcutaneousinjectioninthesubmentalareatohumans
AT parkjinwoo safetytolerabilitypharmacokineticsandpharmacodynamicsofcholicacidmt921afterasubcutaneousinjectioninthesubmentalareatohumans
AT kimdaihyun safetytolerabilitypharmacokineticsandpharmacodynamicsofcholicacidmt921afterasubcutaneousinjectioninthesubmentalareatohumans
AT seosoohong safetytolerabilitypharmacokineticsandpharmacodynamicsofcholicacidmt921afterasubcutaneousinjectioninthesubmentalareatohumans
AT kimkyoungah safetytolerabilitypharmacokineticsandpharmacodynamicsofcholicacidmt921afterasubcutaneousinjectioninthesubmentalareatohumans
AT leewooshun safetytolerabilitypharmacokineticsandpharmacodynamicsofcholicacidmt921afterasubcutaneousinjectioninthesubmentalareatohumans
AT parkjiyoung safetytolerabilitypharmacokineticsandpharmacodynamicsofcholicacidmt921afterasubcutaneousinjectioninthesubmentalareatohumans