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Introduction <p>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&#xa0;months (q2m).</p> Methods <p>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> Results <p>When switching from PP1m 234&#xa0;mg at steady state (comparable to 6&#xa0;mg/day oral risperidone), the most comparable switch involved initiating TV-46000 125&#xa0;mg q1m 4&#xa0;weeks after the last PP1m dose. Ratios of TV-46000 to PP1m for maximum, minimum, and average plasma concentration (<i>C</i><sub>max</sub>, <i>C</i><sub>min</sub>, and <i>C</i><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&#xa0;mg daily oral risperidone) using a 4-week interval demonstrated comparable TAM exposures. When switching from PP1m 234&#xa0;mg to TV-46000 250&#xa0;mg q2m, <i>C</i><sub>max</sub> was higher and <i>C</i><sub>min</sub> lower than that of q1m, though <i>C</i><sub>avg</sub> remained comparable to 5/6&#xa0;mg daily oral risperidone.</p> Conclusion <p>Switching to TV-46000 125&#xa0;mg q1m 4&#xa0;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>

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Switching Patients with Schizophrenia from Intramuscular Paliperidone Palmitate Once Monthly to TV-46000, a Long-Acting Subcutaneous Antipsychotic: Population Pharmacokinetic–Based Strategies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月8日

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  • Itay Perlstein,
  • Jonathan Meyer,
  • Ziqi Yue,
  • Vijay Ivaturi,
  • Kelli R. Franzenburg,
  • Mark Suett,
  • Rolf Hansen,
  • Avia Merenlender Wagner,
  • Arti Phatak,
  • Rajendra Singh

摘要

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.