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Population pharmacokinetic modeling and simulation of immunoglobulin exposure with varying dosing intervals of subcutaneous immunoglobulin 20% (Ig20Gly) in patients with primary immunodeficiency diseases

Dumas, Todd, Berry, N. Seth, Wolfsegger, Martin, Jolles, Stephen, McCoy, Barbara and Yel, Leman 2019. Population pharmacokinetic modeling and simulation of immunoglobulin exposure with varying dosing intervals of subcutaneous immunoglobulin 20% (Ig20Gly) in patients with primary immunodeficiency diseases. International Immunopharmacology 71 , pp. 404-410. 10.1016/j.intimp.2019.03.034

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Abstract

Background Immunoglobulin (IG) replacement therapy in patients with primary immunodeficiency diseases (PID) can be administered daily to every 2 weeks subcutaneously (SCIG) or every 3 or 4 weeks intravenously (IVIG). Objectives Develop a population pharmacokinetic (PK) model simulating IG exposure with Ig20Gly, a 20% SCIG; determine the dose adjustment factor for Ig20Gly relative to IVIG. Methods Data from patients with PID treated with Ig20Gly and IVIG 10% were used to characterize IG population PK by nonlinear mixed-effects modeling and validated using data splitting and a visual predictive check. IG profiles were simulated for 1000 patients/interval treated with Ig20Gly (daily, every 2 days, every 3 days, twice weekly, weekly, every 2 weeks). An Ig20Gly adjustment factor of 130% was used to simulate Ig20Gly to IVIG AUC ratios for weekly or every 2 weeks Ig20Gly dosing intervals and a monthly IVIG dosing interval. Results A 1-compartment model, using weight as a covariate on clearance, derived from an index modeling dataset (n = 81) demonstrated predictability for a validation dataset (n = 21). The model estimate of bioavailability was 73.9%. Simulations for 6 dosing intervals showed similar mean profiles with overlapping prediction intervals. Mean AUC ratios of Ig20Gly to IVIG with a dose adjustment factor of 1.30:1 were 98.7% for weekly and 97.7% for twice-weekly administration demonstrating comparable exposure. Conclusion Ig20Gly exposures from daily to up to every 2 weeks appeared equivalent. A 1.30 conversion factor provided coverage comparable to IVIG when Ig20Gly is administered daily to every 2 weeks.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 1567-5769
Funders: N/A
Date of First Compliant Deposit: 29 April 2019
Date of Acceptance: 19 March 2019
Last Modified: 18 Jun 2019 15:34
URI: http://orca-mwe.cf.ac.uk/id/eprint/121903

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