Management of antipsychotic treatment discontinuation and interruptions using model-based simulations

Mahesh N Samtani,1 John J Sheehan,2 Dong-Jing Fu,2 Bart Remmerie,3 Jennifer Kern Sliwa,2 Larry Alphs21Janssen Research and Development, Raritan, NJ, USA; 2Janssen Scientific Affairs, Titusville, NJ, USA; 3Janssen Research and Development, Division of Janssen Pharmaceutica, Beerse, BelgiumBackground:...

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Autores principales:	Samtani MN, Sheehan JJ, Fu D-J, Remmerie B, Sliwa JK, Alphs L
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2012
Materias:	Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/db918d18b2894760b2d241167c1b2d3b
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spelling	oai:doaj.org-article:db918d18b2894760b2d241167c1b2d3b2021-12-02T02:43:24ZManagement of antipsychotic treatment discontinuation and interruptions using model-based simulations1179-1438https://doaj.org/article/db918d18b2894760b2d241167c1b2d3b2012-07-01T00:00:00Zhttp://www.dovepress.com/management-of-antipsychotic-treatment-discontinuation-and-interruption-a10416https://doaj.org/toc/1179-1438Mahesh N Samtani,1 John J Sheehan,2 Dong-Jing Fu,2 Bart Remmerie,3 Jennifer Kern Sliwa,2 Larry Alphs21Janssen Research and Development, Raritan, NJ, USA; 2Janssen Scientific Affairs, Titusville, NJ, USA; 3Janssen Research and Development, Division of Janssen Pharmaceutica, Beerse, BelgiumBackground: Medication nonadherence is a well described and prevalent clinical occurrence in schizophrenia. These pharmacokinetic model-based simulations analyze predicted antipsychotic plasma concentrations in nonadherence and treatment interruption scenarios and with treatment reinitiation.Methods: Starting from steady state, pharmacokinetic model-based simulations of active moiety plasma concentrations of oral, immediate-release risperidone 3 mg/day, risperidone long-acting injection 37.5 mg/14 days, oral paliperidone extended-release 6 mg/day, and paliperidone palmitate 117 mg (75 mg equivalents)/28 days were assessed under three treatment discontinuation/interruption scenarios, ie, complete discontinuation, one week of interruption, and four weeks of interruption. In the treatment interruption scenarios, pharmacokinetic simulations were performed using medication-specific reinitiation strategies.Results: Following complete treatment discontinuation, plasma concentrations persisted longest with paliperidone palmitate, followed by risperidone long-acting injection, while oral formulations exhibited the most rapid decrease. One week of oral paliperidone or risperidone interruption resulted in near complete elimination from the systemic circulation within that timeframe, reflecting the rapid elimination rate of the active moiety. After 1 and 4 weeks of interruption, minimum plasma concentrations were higher with paliperidone palmitate than risperidone long-acting injection over the simulated period. Four weeks of treatment interruption followed by reinitiation resulted in plasma levels returning to predicted therapeutic levels within 1 week.Conclusion: Due to the long half-life of paliperidone palmitate (25&ndash;49 days), putative therapeutic plasma concentrations persisted longest in simulated cases of complete discontinuation or treatment interruption. These simulations may help clinicians better conceptualize the impact of antipsychotic nonadherence on plasma concentrations, and the impact of medication-specific reinitiation strategies after intermittent nonadherence.Keywords: paliperidone palmitate, risperidone, long-acting injection, pharmacokinetics, nonadherence, plasma concentrationsSamtani MNSheehan JJFu D-JRemmerie BSliwa JKAlphs LDove Medical PressarticleTherapeutics. PharmacologyRM1-950ENClinical Pharmacology: Advances and Applications, Vol 2012, Iss default, Pp 25-40 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950
spellingShingle	Therapeutics. Pharmacology RM1-950 Samtani MN Sheehan JJ Fu D-J Remmerie B Sliwa JK Alphs L Management of antipsychotic treatment discontinuation and interruptions using model-based simulations
description	Mahesh N Samtani,1 John J Sheehan,2 Dong-Jing Fu,2 Bart Remmerie,3 Jennifer Kern Sliwa,2 Larry Alphs21Janssen Research and Development, Raritan, NJ, USA; 2Janssen Scientific Affairs, Titusville, NJ, USA; 3Janssen Research and Development, Division of Janssen Pharmaceutica, Beerse, BelgiumBackground: Medication nonadherence is a well described and prevalent clinical occurrence in schizophrenia. These pharmacokinetic model-based simulations analyze predicted antipsychotic plasma concentrations in nonadherence and treatment interruption scenarios and with treatment reinitiation.Methods: Starting from steady state, pharmacokinetic model-based simulations of active moiety plasma concentrations of oral, immediate-release risperidone 3 mg/day, risperidone long-acting injection 37.5 mg/14 days, oral paliperidone extended-release 6 mg/day, and paliperidone palmitate 117 mg (75 mg equivalents)/28 days were assessed under three treatment discontinuation/interruption scenarios, ie, complete discontinuation, one week of interruption, and four weeks of interruption. In the treatment interruption scenarios, pharmacokinetic simulations were performed using medication-specific reinitiation strategies.Results: Following complete treatment discontinuation, plasma concentrations persisted longest with paliperidone palmitate, followed by risperidone long-acting injection, while oral formulations exhibited the most rapid decrease. One week of oral paliperidone or risperidone interruption resulted in near complete elimination from the systemic circulation within that timeframe, reflecting the rapid elimination rate of the active moiety. After 1 and 4 weeks of interruption, minimum plasma concentrations were higher with paliperidone palmitate than risperidone long-acting injection over the simulated period. Four weeks of treatment interruption followed by reinitiation resulted in plasma levels returning to predicted therapeutic levels within 1 week.Conclusion: Due to the long half-life of paliperidone palmitate (25&ndash;49 days), putative therapeutic plasma concentrations persisted longest in simulated cases of complete discontinuation or treatment interruption. These simulations may help clinicians better conceptualize the impact of antipsychotic nonadherence on plasma concentrations, and the impact of medication-specific reinitiation strategies after intermittent nonadherence.Keywords: paliperidone palmitate, risperidone, long-acting injection, pharmacokinetics, nonadherence, plasma concentrations
format	article
author	Samtani MN Sheehan JJ Fu D-J Remmerie B Sliwa JK Alphs L
author_facet	Samtani MN Sheehan JJ Fu D-J Remmerie B Sliwa JK Alphs L
author_sort	Samtani MN
title	Management of antipsychotic treatment discontinuation and interruptions using model-based simulations
title_short	Management of antipsychotic treatment discontinuation and interruptions using model-based simulations
title_full	Management of antipsychotic treatment discontinuation and interruptions using model-based simulations
title_fullStr	Management of antipsychotic treatment discontinuation and interruptions using model-based simulations
title_full_unstemmed	Management of antipsychotic treatment discontinuation and interruptions using model-based simulations
title_sort	management of antipsychotic treatment discontinuation and interruptions using model-based simulations
publisher	Dove Medical Press
publishDate	2012
url	https://doaj.org/article/db918d18b2894760b2d241167c1b2d3b
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Management of antipsychotic treatment discontinuation and interruptions using model-based simulations

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