Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia
Abstract Introduction TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) agent that combines risperidone and an innovative, copolymer-based drug delivery technology in a suspension suitable for subcutaneous administration from a prefilled syringe. The objective of the current analysis was...
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Adis, Springer Healthcare
2025-03-01
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| Series: | Neurology and Therapy |
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| Online Access: | https://doi.org/10.1007/s40120-025-00723-z |
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| author | Itay Perlstein Avia Merenlender Wagner Anna Elgart Anthe S. Zandvliet Farina Hellmann YuWei Lin Eline van Maanen Nele Plock Floris Fauchet Rajendra Singh |
| author_facet | Itay Perlstein Avia Merenlender Wagner Anna Elgart Anthe S. Zandvliet Farina Hellmann YuWei Lin Eline van Maanen Nele Plock Floris Fauchet Rajendra Singh |
| author_sort | Itay Perlstein |
| collection | DOAJ |
| description | Abstract Introduction TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) agent that combines risperidone and an innovative, copolymer-based drug delivery technology in a suspension suitable for subcutaneous administration from a prefilled syringe. The objective of the current analysis was to characterize the pharmacokinetics (PK) of TV-46000 based on pooled data from phase 1 and phase 3 studies, and to further support clinical use aspects of TV-46000. Methods A population PK (popPK) model was developed using TV-46000 PK data obtained from three phase 1 studies (n = 267) and two phase 3 trials (n = 425). A sequential parent–metabolite model structure was used, and the total active moiety (TAM) concentration–time profiles were simulated for TV-46000 once monthly (q1m) and once every 2 months (q2m) across the range of available doses and different administration sites. Results The popPK model adequately characterized the PK of risperidone and its active metabolite. TV-46000 reaches therapeutic plasma TAM concentrations (≥ 10 ng/mL) within 24 h following first dose administration. Three months after initiation of TV-46000, 86% and 88% of steady-state TAM exposure were achieved for q1m and q2m, respectively, and steady state was fully attained by 6 months (i.e., > 90% of steady-state TAM exposure). In addition, simulated D2 receptor occupancy for TV-46000 was generally within the therapeutic window of 60–80% during both dosing intervals. Conclusions The developed popPK model, together with corresponding simulations, supports TV-46000 as a LASCA that offers flexible dosing intervals (q1m or q2m) and administration sites (abdomen or upper arm) and does not require oral supplementation or loading dose(s). |
| format | Article |
| id | doaj-art-263ed3bec9764330b65acd3b61580e8b |
| institution | DOAJ |
| issn | 2193-8253 2193-6536 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Adis, Springer Healthcare |
| record_format | Article |
| series | Neurology and Therapy |
| spelling | doaj-art-263ed3bec9764330b65acd3b61580e8b2025-08-20T03:08:28ZengAdis, Springer HealthcareNeurology and Therapy2193-82532193-65362025-03-0114382984810.1007/s40120-025-00723-zPopulation Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with SchizophreniaItay Perlstein0Avia Merenlender Wagner1Anna Elgart2Anthe S. Zandvliet3Farina Hellmann4YuWei Lin5Eline van Maanen6Nele Plock7Floris Fauchet8Rajendra Singh9Magic Wand Research LLCTeva Pharmaceutical Industries Ltd., Quantitative Pharmacology and Biosimilar SciencesTeva Pharmaceutical Industries Ltd., Innovative Medicines, Global Clinical DevelopmentCertaraCertaraCertaraCertaraCertaraCertaraTeva Branded Pharmaceuticals LLC, Quantitative Pharmacology and Biosimilar SciencesAbstract Introduction TV-46000 is a long-acting subcutaneous antipsychotic (LASCA) agent that combines risperidone and an innovative, copolymer-based drug delivery technology in a suspension suitable for subcutaneous administration from a prefilled syringe. The objective of the current analysis was to characterize the pharmacokinetics (PK) of TV-46000 based on pooled data from phase 1 and phase 3 studies, and to further support clinical use aspects of TV-46000. Methods A population PK (popPK) model was developed using TV-46000 PK data obtained from three phase 1 studies (n = 267) and two phase 3 trials (n = 425). A sequential parent–metabolite model structure was used, and the total active moiety (TAM) concentration–time profiles were simulated for TV-46000 once monthly (q1m) and once every 2 months (q2m) across the range of available doses and different administration sites. Results The popPK model adequately characterized the PK of risperidone and its active metabolite. TV-46000 reaches therapeutic plasma TAM concentrations (≥ 10 ng/mL) within 24 h following first dose administration. Three months after initiation of TV-46000, 86% and 88% of steady-state TAM exposure were achieved for q1m and q2m, respectively, and steady state was fully attained by 6 months (i.e., > 90% of steady-state TAM exposure). In addition, simulated D2 receptor occupancy for TV-46000 was generally within the therapeutic window of 60–80% during both dosing intervals. Conclusions The developed popPK model, together with corresponding simulations, supports TV-46000 as a LASCA that offers flexible dosing intervals (q1m or q2m) and administration sites (abdomen or upper arm) and does not require oral supplementation or loading dose(s).https://doi.org/10.1007/s40120-025-00723-zTV-46000SchizophreniaPopulation pharmacokinetic modelingRisperidoneLong-acting subcutaneous antipsychotic |
| spellingShingle | Itay Perlstein Avia Merenlender Wagner Anna Elgart Anthe S. Zandvliet Farina Hellmann YuWei Lin Eline van Maanen Nele Plock Floris Fauchet Rajendra Singh Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia Neurology and Therapy TV-46000 Schizophrenia Population pharmacokinetic modeling Risperidone Long-acting subcutaneous antipsychotic |
| title | Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia |
| title_full | Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia |
| title_fullStr | Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia |
| title_full_unstemmed | Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia |
| title_short | Population Pharmacokinetic Modeling of TV-46000, a Risperidone Long-Acting Subcutaneous Antipsychotic for the Treatment of Patients with Schizophrenia |
| title_sort | population pharmacokinetic modeling of tv 46000 a risperidone long acting subcutaneous antipsychotic for the treatment of patients with schizophrenia |
| topic | TV-46000 Schizophrenia Population pharmacokinetic modeling Risperidone Long-acting subcutaneous antipsychotic |
| url | https://doi.org/10.1007/s40120-025-00723-z |
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