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Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes.

Urien S, Bardin C, Bader-Meunier B, Mouy R, Compeyrot-Lacassagne S, Foissac F, Florkin B, Wouters C, Neven B, Treluyer JM, Quartier P - BMC Pharmacol Toxicol (2013)

Bottom Line: Taking into account bodyweight to explain variations in apparent clearance (CL/F) and distribution volume (V/F) significantly reduced the associated between-subject and between-occasion variabilities.There was no significant effect of the combined anti-inflammatory treatment.The proportion of patients for which the development of a resistance to treatment was significant was 62% and the corresponding time was approximately 60 days.

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ABSTRACT

Background: Anakinra pharmacokinetics and pharmacodynamics were investigated in children and adolescents treated for systemic-onset juvenile idiopathic arthritis (SJIA) and autoinflammatory syndromes.

Methods: Anakinra was given subcutaneously at doses between 2 and 10 mg/kg (maximum 100 mg) per day. Anakinra concentrations were recorded in patients, as well as C-reactive protein (CRP) levels, on different occasions. The data were fitted to a pharmacokinetic-pharmacodynamic model via a population approach using Monolix.

Results: A total of 87 children and adolescents, 8 months to 21 years old, were available for pharmacokinetic evaluation. A one compartment model with linear absorption and elimination described the pharmacokinetics. Taking into account bodyweight to explain variations in apparent clearance (CL/F) and distribution volume (V/F) significantly reduced the associated between-subject and between-occasion variabilities. The final estimates were 6.24 L/h/70 kg and 65.2 L/70 kg for CL/F and V/F respectively. A mixture pharmacodynamic model described the CRP level change during anakinra treatment for the SJIA patients with 2 subpopulations, patients with high baseline and large CRP decrease and patients with low baseline and small CRP decrease followed by a re-increase in CRP levels. There was no significant effect of the combined anti-inflammatory treatment. The proportion of patients for which the development of a resistance to treatment was significant was 62% and the corresponding time was approximately 60 days.

Conclusions: Based on effects in SJIA, a prospective dosage adjustment was proposed based on a 0.4 mg/L Css target in order to obtain a CRP decrease to 10 mg/L or below.

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Anakinra concentration-time courses for once daily administrations. Solid and dashed lines, median and 5th/95th percentiles of the final model predictions.
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Figure 1: Anakinra concentration-time courses for once daily administrations. Solid and dashed lines, median and 5th/95th percentiles of the final model predictions.

Mentions: A total of 87 children (32 girls, 52 boys) with 148 anakinra concentrations were available for pharmacokinetic evaluation, four concentrations were observed below the limit of quantification (BLQ) and coded as left censored data for the analysis. The distribution of sampling times can be observed in FigureĀ 1.


Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes.

Urien S, Bardin C, Bader-Meunier B, Mouy R, Compeyrot-Lacassagne S, Foissac F, Florkin B, Wouters C, Neven B, Treluyer JM, Quartier P - BMC Pharmacol Toxicol (2013)

Anakinra concentration-time courses for once daily administrations. Solid and dashed lines, median and 5th/95th percentiles of the final model predictions.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750485&req=5

Figure 1: Anakinra concentration-time courses for once daily administrations. Solid and dashed lines, median and 5th/95th percentiles of the final model predictions.
Mentions: A total of 87 children (32 girls, 52 boys) with 148 anakinra concentrations were available for pharmacokinetic evaluation, four concentrations were observed below the limit of quantification (BLQ) and coded as left censored data for the analysis. The distribution of sampling times can be observed in FigureĀ 1.

Bottom Line: Taking into account bodyweight to explain variations in apparent clearance (CL/F) and distribution volume (V/F) significantly reduced the associated between-subject and between-occasion variabilities.There was no significant effect of the combined anti-inflammatory treatment.The proportion of patients for which the development of a resistance to treatment was significant was 62% and the corresponding time was approximately 60 days.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Anakinra pharmacokinetics and pharmacodynamics were investigated in children and adolescents treated for systemic-onset juvenile idiopathic arthritis (SJIA) and autoinflammatory syndromes.

Methods: Anakinra was given subcutaneously at doses between 2 and 10 mg/kg (maximum 100 mg) per day. Anakinra concentrations were recorded in patients, as well as C-reactive protein (CRP) levels, on different occasions. The data were fitted to a pharmacokinetic-pharmacodynamic model via a population approach using Monolix.

Results: A total of 87 children and adolescents, 8 months to 21 years old, were available for pharmacokinetic evaluation. A one compartment model with linear absorption and elimination described the pharmacokinetics. Taking into account bodyweight to explain variations in apparent clearance (CL/F) and distribution volume (V/F) significantly reduced the associated between-subject and between-occasion variabilities. The final estimates were 6.24 L/h/70 kg and 65.2 L/70 kg for CL/F and V/F respectively. A mixture pharmacodynamic model described the CRP level change during anakinra treatment for the SJIA patients with 2 subpopulations, patients with high baseline and large CRP decrease and patients with low baseline and small CRP decrease followed by a re-increase in CRP levels. There was no significant effect of the combined anti-inflammatory treatment. The proportion of patients for which the development of a resistance to treatment was significant was 62% and the corresponding time was approximately 60 days.

Conclusions: Based on effects in SJIA, a prospective dosage adjustment was proposed based on a 0.4 mg/L Css target in order to obtain a CRP decrease to 10 mg/L or below.

Show MeSH
Related in: MedlinePlus