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Clin Pharmacol Ther. 2017 Oct;102(4):671-678. doi: 10.1002/cpt.686. Epub 2017 May 26.

Eculizumab Dosing Regimen in Atypical HUS: Possibilities for Individualized Treatment.

Author information

1
Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, The Netherlands.
2
Department of Laboratory Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
3
Department of Health Evidence, Radboud University Medical Center, Nijmegen, The Netherlands.
4
Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.
5
Department of Nephrology, Radboud University Medical Center, Nijmegen, The Netherlands.
6
Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.

Abstract

Recent studies indicate that eculizumab is often given in excess to atypical hemolytic uremic syndrome (aHUS) patients. Individualization of treatment is thus highly requested; however, data on the pharmacokinetics and pharmacodynamics of eculizumab remain limited. We analyzed 11 patients during induction (weekly), maintenance (2-weekly), and tapering (every 3-8 weeks) phases of treatment. The trough eculizumab levels increased with each additional dose during the induction phase (depending on body weight). During maintenance, high eculizumab concentrations of up to 772 μg/mL were observed. The levels decreased with each following dose during tapering (3- and 4-week intervals); however, three patients maintained target eculizumab levels over long time periods (30-48 weeks). At intervals of 6-8 weeks, target eculizumab levels were no longer attained. Serum samples with eculizumab concentrations ≥50 μg/mL showed adequate complement blockade. Our data provide essential insight for optimization of eculizumab dosing schemes and lessening of therapy burden for the patients and cost of the treatment.

PMID:
28295239
DOI:
10.1002/cpt.686
[Indexed for MEDLINE]

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