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21.08.2018 | Original Research Article

Intra-monocyte Pharmacokinetics of Imiglucerase Supports a Possible Personalized Management of Gaucher Disease Type 1

Clinical Pharmacokinetics
Juliette Berger, Marie Vigan, Bruno Pereira, Thu Thuy Nguyen, Roseline Froissart, Nadia Belmatoug, Florence Dalbiès, Agathe Masseau, Christian Rose, Christine Serratrice, Yves-Marie Pers, Ivan Bertchansky, Fabrice Camou, Monia Bengherbia, Céline Bourgne, Catherine Caillaud, Magali Pettazzoni, Amina Berrahal, Jérôme Stirnemann, France Mentré, Marc G. Berger
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s40262-018-0708-8) contains supplementary material, which is available to authorized users.
Juliette Berger and Marie Vigan contributed equally to this study.
Juliette Berger, Roseline Froissart, Nadia Belmatoug, Florence Dalbiès, Agathe Masseau, Christian Rose, Christine Serratrice, Fabrice Camou, Monia Bengherbia, Catherine Caillaud, Jérôme Stirnemann, Marc G. Berger: Member of the French group of Gaucher disease experts, CETG (Comité d’Evaluation du Traitement de la maladie de Gaucher).


Background and objectives

Intravenous imiglucerase enzyme replacement therapy for Gaucher disease type 1 administered every 2 weeks is at variance with the imiglucerase plasma half-life of a few minutes. We hypothesized that studying the pharmacokinetics of imiglucerase in blood Gaucher disease type 1 monocytes would be more relevant for understanding enzyme replacement therapy responses.


Glucocerebrosidase intra-monocyte activity was studied by flow cytometry. The pharmacokinetics of imiglucerase was analyzed using a population-pharmacokinetic model from a cohort of 31 patients with Gaucher disease type 1 who either started or were receiving long-term treatment with imiglucerase.


A pharmacokinetic analysis of imiglucerase showed a two-compartment model with a high peak followed by a two-phase exponential decay (fast phase half-life: 0.36 days; slow phase half-life: 9.7 days) leading to a median 1.4-fold increase in glucocerebrosidase intra-monocyte activity from the pre-treatment activity (p = 0.04). In patients receiving long-term treatment, for whom the imiglucerase dose per infusion was chosen on the basis of disease aggressiveness/response, imiglucerase clearance correlated with the administered dose. However, the residual glucocerebrosidase intra-monocyte activity value was dose independent, suggesting that the maintenance of imiglucerase residual activity is patient specific. Endogenous pre-treatment glucocerebrosidase intra-monocyte activity was the most informative single parameter for distinguishing patients without (n = 10) and with a clinical indication (n = 17) for starting enzyme replacement therapy (area under the receiver operating characteristic curve: 0.912; 95% confidence interval 0.8–1; p < 0.001), as confirmed also by a factorial analysis of mixed data.


This study provides novel pharmacokinetic data that support current imiglucerase administration regimens and suggests the existence of a glucocerebrosidase activity threshold related to Gaucher disease type 1 aggressiveness. These findings can potentially improve Gaucher disease type 1 management algorithms and clinical decision making.

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Supplementary material 1 (DOC 979 kb)
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