Bibliographic Details
| Title: |
Physiologically-Based Pharmacokinetic Modeling and In Vitro–In Vivo Correlation of TV-46000 (Risperidone LAI): Prediction from Dog to Human |
| Authors: |
David Bibi, Raphael Bilgraer, Lilach Steiner, Hussein Hallak |
| Source: |
Pharmaceutics, Vol 16, Iss 7, p 896 (2024) |
| Publisher Information: |
MDPI AG, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Pharmacy and materia medica |
| Subject Terms: |
physiologically-based pharmacokinetic modeling (PBPK), in vitro–in vivo correlation (IVIVC), long-acting injectable (LAI), TV-46000, risperidone, schizophrenia, Pharmacy and materia medica, RS1-441 |
| More Details: |
The interest in the development and therapeutic application of long-acting injectable products for chronic or long-term treatments has experienced exponential growth in recent decades. TV-46000 (Uzedy, Teva) is a long-acting subcutaneous (sc) injectable formulation of risperidone, approved for the treatment of schizophrenia in adults. Following sc injection, the copolymers together with risperidone precipitate to form a sc depot under the skin to deliver therapeutic levels of risperidone over a prolonged period of either 1 month or 2 months, depending upon the dose. This work presents the strategy and the results of the physiologically-based pharmacokinetic (PBPK) modeling and establishing of in vitro–in vivo correlation (IVIVC) for the prediction of TV-46000 pharmacokinetic profile in humans, using in vitro release, intravenous (iv), and sc single-dose pharmacokinetic data in beagle dogs. The resulting simulated TV-46000 PK profile in humans showed that the shape of the predicted risperidone and its active metabolite 9-OH-risperidone PK profiles was different from the observed one, thus suggesting that the TV-46000 release profile was species-dependent and cannot be directly extrapolated from dog to human. In conclusion, while level A IVIVC cannot be claimed, this work combining PBPK and IVIVC modeling represents an interesting alternative approach for complex injectable formulations where classical methods are not applicable. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1999-4923 |
| Relation: |
https://www.mdpi.com/1999-4923/16/7/896; https://doaj.org/toc/1999-4923 |
| DOI: |
10.3390/pharmaceutics16070896 |
| Access URL: |
https://doaj.org/article/e6298492b68d4b7592574b3b7f693b17 |
| Accession Number: |
edsdoj.6298492b68d4b7592574b3b7f693b17 |
| Database: |
Directory of Open Access Journals |
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