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Development of a population pharmacokinetic model for the novel long-acting injectable antipsychotic risperidone ISM®.
Laveille, Christian; Snoeck, Eric; Ochoa Díaz de Monasterioguren, Lourdes; Martínez-González, Javier; Llaudó, Jordi; Anta, Lourdes; Gutierro, Ibon.
Afiliação
  • Laveille C; Calvagone SAS, Liergues, France.
  • Snoeck E; Luccio bv, Retie, Belgium.
  • Ochoa Díaz de Monasterioguren L; Laboratorios Farmacéuticos ROVI, S.A., Madrid, Spain.
  • Martínez-González J; Laboratorios Farmacéuticos ROVI, S.A., Madrid, Spain.
  • Llaudó J; Laboratorios Farmacéuticos ROVI, S.A., Madrid, Spain.
  • Anta L; Laboratorios Farmacéuticos ROVI, S.A., Madrid, Spain.
  • Gutierro I; Laboratorios Farmacéuticos ROVI, S.A., Madrid, Spain.
Br J Clin Pharmacol ; 90(9): 2256-2270, 2024 Sep.
Article em En | MEDLINE | ID: mdl-38866397
ABSTRACT

AIMS:

The aims of this study were to develop a population pharmacokinetic (PK) model for risperidone ISM® and to investigate the relationships between active moiety exposure, as described by apparent clearance (CL40), and several covariates using all data from five clinical studies.

METHODS:

A population PK model was developed using active moiety concentrations from a study in healthy volunteers and two studies in patients with schizophrenia. Data from a comparative bioavailability study in medically stable patients and a Phase III study in patients with acute exacerbation of schizophrenia were then incorporated, using empirical Bayesian feedback and model refinement in NONMEM. Finally, covariate analysis was performed on CL40.

RESULTS:

The final model adequately described the pharmacokinetics of 6288 active moiety concentrations in 17 healthy volunteers and 430 patients with schizophrenia. This one-compartment disposition model had a complex absorption process, combining a small amount immediately entering the central active moiety compartment, two first-order absorption processes and a combined zero-order and first order process, with first-order elimination from the central compartment. Significant covariates on CL40 were BMI and sex. Goodness-of-fit (GOF) plots and visual predictive checks (VPC) confirmed acceptable description of the data.

CONCLUSIONS:

The population PK model adequately described active moiety concentrations from five clinical studies after risperidone ISM® administration. Relationships between active moiety exposure and covariates were defined in order to facilitate simulations for future studies. The model showed that risperidone ISM® rapidly achieves therapeutic plasma levels within the first hours after the first injection that are maintained sustainedly throughout the whole dosing interval following once-monthly gluteal injections of 100 mg and 75 mg.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esquizofrenia / Antipsicóticos / Risperidona / Preparações de Ação Retardada / Modelos Biológicos Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Br J Clin Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Esquizofrenia / Antipsicóticos / Risperidona / Preparações de Ação Retardada / Modelos Biológicos Limite: Adolescent / Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Br J Clin Pharmacol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: França