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A comparison of continuous subcutaneous paliperidone infusion and repeated subcutaneous injection of risperidone free-base in rats

Published online by Cambridge University Press:  16 April 2020

G. Marchese
Affiliation:
National Research Council (C.N.R), Institute of Biomedical Technology, Sect. Cagliari, Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
B. Pittau
Affiliation:
PharmaNess S.c.a.r.l., Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
G. Casu
Affiliation:
PharmaNess S.c.a.r.l., Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
G. Peddio
Affiliation:
PharmaNess S.c.a.r.l., Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
G.P. Spada
Affiliation:
National Research Council (C.N.R), Institute of Biomedical Technology, Sect. Cagliari, Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
M. Pira
Affiliation:
PharmaNess S.c.a.r.l., Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
A. Deriu
Affiliation:
National Research Council (C.N.R), Institute of Biomedical Technology, Sect. Cagliari, Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
F. Portesani
Affiliation:
PharmaNess S.c.a.r.l., Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
C. Pisu
Affiliation:
PharmaNess S.c.a.r.l., Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
P. Lazzari
Affiliation:
PharmaNess S.c.a.r.l., Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
L. Pani
Affiliation:
National Research Council (C.N.R), Institute of Biomedical Technology, Sect. Cagliari, Technological Park of Sardinia Sardegna Ricerche, Building 5, Loc. Piscinamanna, 09010Pula, Cagliari, Italy
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Abstract

It is proposed that to achieve a therapeutic effect in schizophrenia patients, dopamine D2-receptor occupancy by antipsychotics within the striatum must exceed 60−65%. However, at high levels of D2-receptor occupancy, the risk of extrapyramidal symptoms (EPS) is increased. Following oral dosing of antipsychotics, peaks and troughs in plasma drug concentrations may be mirrored by fluctuations in D2-receptor occupancy. Paliperidone, a novel antipsychotic available as extended-release tablets (paliperidone ER), is the major active metabolite of risperidone and exhibits a plasma pharmacokinetic profile with reduced peak−trough fluctuations and consistent D2-receptor occupancy compared with conventional oral antipsychotic formulations. Using formulations that resemble those in clinical practice, this study provides a preclinical evaluation of the pharmacological properties of paliperidone ER and risperidone immediate-release formulation in terms of consistent antipsychotic efficacy over time and extrapyramidal symptom liability. Significant fluctuations in inhibition of d-amphetamine-induced hyperlocomotion were observed for repeated subcutaneous (SC) risperidone injections, whereas stable inhibitory efficacy was demonstrated during continuous SC paliperidone infusion. Similarly, significant fluctuations in latency on-bar were observed with repeated SC risperidone injections, whereas significantly lower latency on-bar was demonstrated following continuous SC paliperidone infusion. These results in an animal model suggest that although risperidone and paliperidone demonstrate similar pharmacologic effects, continuous administration of paliperidone achieves more stable antipsychotic efficacy with reduced motor impairment, akin to the effects observed with paliperidone ER in clinical studies.

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Original articles
Copyright
Copyright © Elsevier Masson SAS 2010

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A comparison of continuous subcutaneous paliperidone infusion and repeated subcutaneous injection of risperidone free-base in rats
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