Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic Models
MT921 is a new injectable drug developed by Medytox Inc. to reduce submental fat. Cholic acid is the active pharmaceutical ingredient, a primary bile acid biosynthesized from cholesterol, endogenously produced by liver in humans and other mammals. Although individuals treated with MT921 could be adm...
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| Format: | Article |
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MDPI AG
2021-07-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/14/7/654 |
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| author | Hyo-jeong Ryu Hyun-ki Moon Junho Lee Gi-hyeok Yang Sung-yoon Yang Hwi-yeol Yun Jung-woo Chae Won-ho Kang |
| author_facet | Hyo-jeong Ryu Hyun-ki Moon Junho Lee Gi-hyeok Yang Sung-yoon Yang Hwi-yeol Yun Jung-woo Chae Won-ho Kang |
| author_sort | Hyo-jeong Ryu |
| collection | DOAJ |
| description | MT921 is a new injectable drug developed by Medytox Inc. to reduce submental fat. Cholic acid is the active pharmaceutical ingredient, a primary bile acid biosynthesized from cholesterol, endogenously produced by liver in humans and other mammals. Although individuals treated with MT921 could be administered with multiple medications, such as those for hypertension, diabetes, and hyperlipidemia, the pharmacokinetic drug–drug interaction (DDI) has not been investigated yet. Therefore, we studied in vitro against drug-metabolizing enzymes and transporters. Moreover, we predicted the potential DDI between MT921 and drugs for chronic diseases using physiologically-based pharmacokinetic (PBPK) modeling and simulation. The magnitude of DDI was found to be negligible in in vitro inhibition and induction of cytochrome P450s and UDP-glucuronosyltransferases. Organic anion transporting polypeptide (OATP)1B3, organic anion transporter (OAT)3, Na<sup>+</sup>-taurocholate cotransporting polypeptide (NTCP), and apical sodium-dependent bile acid transporter (ASBT) are mainly involved in MT921 transport. Based on the result of in vitro experiments, the PBPK model of MT921 was developed and evaluated by clinical data. Furthermore, the PBPK model of amlodipine was developed and evaluated. PBPK DDI simulation results indicated that the pharmacokinetics of MT921 was not affected by the perpetrator drugs. In conclusion, MT921 could be administered without a DDI risk based on in vitro study and related in silico simulation. Further clinical studies are needed to validate this finding. |
| first_indexed | 2024-03-10T09:29:04Z |
| format | Article |
| id | doaj.art-eadca2796e2d4fa39a4261628d167170 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T09:29:04Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-eadca2796e2d4fa39a4261628d1671702023-11-22T04:39:41ZengMDPI AGPharmaceuticals1424-82472021-07-0114765410.3390/ph14070654Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic ModelsHyo-jeong Ryu0Hyun-ki Moon1Junho Lee2Gi-hyeok Yang3Sung-yoon Yang4Hwi-yeol Yun5Jung-woo Chae6Won-ho Kang7Gwangkyo R&D Center, Medytox Inc., Suwon 16506, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaGwangkyo R&D Center, Medytox Inc., Suwon 16506, KoreaGwangkyo R&D Center, Medytox Inc., Suwon 16506, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaCollege of Pharmacy, Chungnam National University, Daejeon 34134, KoreaGwangkyo R&D Center, Medytox Inc., Suwon 16506, KoreaMT921 is a new injectable drug developed by Medytox Inc. to reduce submental fat. Cholic acid is the active pharmaceutical ingredient, a primary bile acid biosynthesized from cholesterol, endogenously produced by liver in humans and other mammals. Although individuals treated with MT921 could be administered with multiple medications, such as those for hypertension, diabetes, and hyperlipidemia, the pharmacokinetic drug–drug interaction (DDI) has not been investigated yet. Therefore, we studied in vitro against drug-metabolizing enzymes and transporters. Moreover, we predicted the potential DDI between MT921 and drugs for chronic diseases using physiologically-based pharmacokinetic (PBPK) modeling and simulation. The magnitude of DDI was found to be negligible in in vitro inhibition and induction of cytochrome P450s and UDP-glucuronosyltransferases. Organic anion transporting polypeptide (OATP)1B3, organic anion transporter (OAT)3, Na<sup>+</sup>-taurocholate cotransporting polypeptide (NTCP), and apical sodium-dependent bile acid transporter (ASBT) are mainly involved in MT921 transport. Based on the result of in vitro experiments, the PBPK model of MT921 was developed and evaluated by clinical data. Furthermore, the PBPK model of amlodipine was developed and evaluated. PBPK DDI simulation results indicated that the pharmacokinetics of MT921 was not affected by the perpetrator drugs. In conclusion, MT921 could be administered without a DDI risk based on in vitro study and related in silico simulation. Further clinical studies are needed to validate this finding.https://www.mdpi.com/1424-8247/14/7/654MT921drug–drug interactionin vitro studiestransporterphysiologically-based pharmacokinetic model |
| spellingShingle | Hyo-jeong Ryu Hyun-ki Moon Junho Lee Gi-hyeok Yang Sung-yoon Yang Hwi-yeol Yun Jung-woo Chae Won-ho Kang Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic Models Pharmaceuticals MT921 drug–drug interaction in vitro studies transporter physiologically-based pharmacokinetic model |
| title | Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic Models |
| title_full | Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic Models |
| title_fullStr | Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic Models |
| title_full_unstemmed | Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic Models |
| title_short | Evaluation for Potential Drug–Drug Interaction of MT921 Using In Vitro Studies and Physiologically–Based Pharmacokinetic Models |
| title_sort | evaluation for potential drug drug interaction of mt921 using in vitro studies and physiologically based pharmacokinetic models |
| topic | MT921 drug–drug interaction in vitro studies transporter physiologically-based pharmacokinetic model |
| url | https://www.mdpi.com/1424-8247/14/7/654 |
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