Itay Perlstein, Jonathan Meyer, Ziqi Yue, Vijay Ivaturi, Kelli R Franzenburg, Mark Suett, Rolf Hansen, Avia Merenlender Wagner, Arti Phatak, Rajendra Singh
{"title":"将精神分裂症患者从肌注棕榈酸帕利哌酮每月一次改为长效皮下抗精神病药tvs -46000：基于人群药代动力学的策略","authors":"Itay Perlstein, Jonathan Meyer, Ziqi Yue, Vijay Ivaturi, Kelli R Franzenburg, Mark Suett, Rolf Hansen, Avia Merenlender Wagner, Arti Phatak, Rajendra Singh","doi":"10.1007/s12325-025-03329-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Pharmacokinetic differences between long-acting injectable antipsychotic (LAI) formulations, combined with a lack of clinical switch studies, contribute to clinician uncertainty when transitioning between LAIs. This analysis employed a population pharmacokinetic (popPK) modeling approach to characterize dosing conversions and switching strategies from intramuscular paliperidone palmitate once monthly (PP1m) to TV-46000, a long-acting subcutaneous formulation of risperidone, once monthly (q1m), with a secondary analysis of PP1m to TV-46000 every 2 months (q2m).</p><p><strong>Methods: </strong>For PP1m and TV-46000, concentration-time profiles for paliperidone and TV-46000 total active moiety (TAM; risperidone + paliperidone) were simulated on the basis of published popPK models with virtual populations of 5000 patients. TAM exposure following oral administration served as a comparison benchmark.</p><p><strong>Results: </strong>When switching from PP1m 234 mg at steady state (comparable to 6 mg/day oral risperidone), the most comparable switch involved initiating TV-46000 125 mg q1m 4 weeks after the last PP1m dose. Ratios of TV-46000 to PP1m for maximum, minimum, and average plasma concentration (C<sub>max</sub>, C<sub>min</sub>, and C<sub>avg</sub>, respectively) post switch ranged from 1.0 to 1.4 after the first dose and 1.0-1.3 at steady state. Switching from other PP1m doses to TV-46000 q1m (comparable to 2-4 mg daily oral risperidone) using a 4-week interval demonstrated comparable TAM exposures. When switching from PP1m 234 mg to TV-46000 250 mg q2m, C<sub>max</sub> was higher and C<sub>min</sub> lower than that of q1m, though C<sub>avg</sub> remained comparable to 5/6 mg daily oral risperidone.</p><p><strong>Conclusion: </strong>Switching to TV-46000 125 mg q1m 4 weeks after the last PP1m 234-mg injection yielded generally comparable pharmacokinetic parameters at steady state. The same was true for other TV-46000 q1m or q2m dosages and equivalent dosages of PP1m. Clinician discretion will ultimately determine how to switch on the basis of factors such as patient preference, convenience, and concerns about tolerability or symptom breakthrough.</p>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":" ","pages":""},"PeriodicalIF":4.0000,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Switching Patients with Schizophrenia from Intramuscular Paliperidone Palmitate Once Monthly to TV-46000, a Long-Acting Subcutaneous Antipsychotic: Population Pharmacokinetic-Based Strategies.\",\"authors\":\"Itay Perlstein, Jonathan Meyer, Ziqi Yue, Vijay Ivaturi, Kelli R Franzenburg, Mark Suett, Rolf Hansen, Avia Merenlender Wagner, Arti Phatak, Rajendra Singh\",\"doi\":\"10.1007/s12325-025-03329-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Pharmacokinetic differences between long-acting injectable antipsychotic (LAI) formulations, combined with a lack of clinical switch studies, contribute to clinician uncertainty when transitioning between LAIs. This analysis employed a population pharmacokinetic (popPK) modeling approach to characterize dosing conversions and switching strategies from intramuscular paliperidone palmitate once monthly (PP1m) to TV-46000, a long-acting subcutaneous formulation of risperidone, once monthly (q1m), with a secondary analysis of PP1m to TV-46000 every 2 months (q2m).</p><p><strong>Methods: </strong>For PP1m and TV-46000, concentration-time profiles for paliperidone and TV-46000 total active moiety (TAM; risperidone + paliperidone) were simulated on the basis of published popPK models with virtual populations of 5000 patients. TAM exposure following oral administration served as a comparison benchmark.</p><p><strong>Results: </strong>When switching from PP1m 234 mg at steady state (comparable to 6 mg/day oral risperidone), the most comparable switch involved initiating TV-46000 125 mg q1m 4 weeks after the last PP1m dose. Ratios of TV-46000 to PP1m for maximum, minimum, and average plasma concentration (C<sub>max</sub>, C<sub>min</sub>, and C<sub>avg</sub>, respectively) post switch ranged from 1.0 to 1.4 after the first dose and 1.0-1.3 at steady state. Switching from other PP1m doses to TV-46000 q1m (comparable to 2-4 mg daily oral risperidone) using a 4-week interval demonstrated comparable TAM exposures. When switching from PP1m 234 mg to TV-46000 250 mg q2m, C<sub>max</sub> was higher and C<sub>min</sub> lower than that of q1m, though C<sub>avg</sub> remained comparable to 5/6 mg daily oral risperidone.</p><p><strong>Conclusion: </strong>Switching to TV-46000 125 mg q1m 4 weeks after the last PP1m 234-mg injection yielded generally comparable pharmacokinetic parameters at steady state. The same was true for other TV-46000 q1m or q2m dosages and equivalent dosages of PP1m. Clinician discretion will ultimately determine how to switch on the basis of factors such as patient preference, convenience, and concerns about tolerability or symptom breakthrough.</p>\",\"PeriodicalId\":7482,\"journal\":{\"name\":\"Advances in Therapy\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-09-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Advances in Therapy\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12325-025-03329-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Advances in Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12325-025-03329-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Switching Patients with Schizophrenia from Intramuscular Paliperidone Palmitate Once Monthly to TV-46000, a Long-Acting Subcutaneous Antipsychotic: Population Pharmacokinetic-Based Strategies.
Introduction: Pharmacokinetic differences between long-acting injectable antipsychotic (LAI) formulations, combined with a lack of clinical switch studies, contribute to clinician uncertainty when transitioning between LAIs. This analysis employed a population pharmacokinetic (popPK) modeling approach to characterize dosing conversions and switching strategies from intramuscular paliperidone palmitate once monthly (PP1m) to TV-46000, a long-acting subcutaneous formulation of risperidone, once monthly (q1m), with a secondary analysis of PP1m to TV-46000 every 2 months (q2m).
Methods: For PP1m and TV-46000, concentration-time profiles for paliperidone and TV-46000 total active moiety (TAM; risperidone + paliperidone) were simulated on the basis of published popPK models with virtual populations of 5000 patients. TAM exposure following oral administration served as a comparison benchmark.
Results: When switching from PP1m 234 mg at steady state (comparable to 6 mg/day oral risperidone), the most comparable switch involved initiating TV-46000 125 mg q1m 4 weeks after the last PP1m dose. Ratios of TV-46000 to PP1m for maximum, minimum, and average plasma concentration (Cmax, Cmin, and Cavg, respectively) post switch ranged from 1.0 to 1.4 after the first dose and 1.0-1.3 at steady state. Switching from other PP1m doses to TV-46000 q1m (comparable to 2-4 mg daily oral risperidone) using a 4-week interval demonstrated comparable TAM exposures. When switching from PP1m 234 mg to TV-46000 250 mg q2m, Cmax was higher and Cmin lower than that of q1m, though Cavg remained comparable to 5/6 mg daily oral risperidone.
Conclusion: Switching to TV-46000 125 mg q1m 4 weeks after the last PP1m 234-mg injection yielded generally comparable pharmacokinetic parameters at steady state. The same was true for other TV-46000 q1m or q2m dosages and equivalent dosages of PP1m. Clinician discretion will ultimately determine how to switch on the basis of factors such as patient preference, convenience, and concerns about tolerability or symptom breakthrough.
期刊介绍：
Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.
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