Population Pharmacokinetics of Alemtuzumab (Campath) in Pediatric Hematopoietic Cell Transplantation: Towards Individualized Dosing to Improve Outcome

Rick Admiraal, Cornelia M Jol-van der Zijde, Juliana M Furtado Silva, Catherijne A J Knibbe, Arjan C Lankester, Jaap Jan Boelens, Goeff Hale, Aniekan Etuk, Melanie Wilson, Stuart Adams, Paul Veys, Charlotte van Kesteren, Robbert G M Bredius

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

Samenvatting

BACKGROUND AND OBJECTIVE: Alemtuzumab (Campath®) is used to prevent graft-versus-host disease and graft failure following pediatric allogeneic hematopoietic cell transplantation. The main toxicity includes delayed immune reconstitution, subsequent viral reactivations, and leukemia relapse. Exposure to alemtuzumab is highly variable upon empirical milligram/kilogram dosing.

METHODS: A population pharmacokinetic (PK) model for alemtuzumab was developed based on a total of 1146 concentration samples from 206 patients, aged 0.2-19 years, receiving a cumulative intravenous dose of 0.2-1.5 mg/kg, and treated between 2003 and 2015 in two centers.

RESULTS: Alemtuzumab PK were best described using a two-compartment model with a parallel saturable and linear elimination pathway. The linear clearance pathway, central volume of distribution, and intercompartmental distribution increased with body weight. Blood lymphocyte counts, a potential substrate for alemtuzumab, did not impact clearance.

CONCLUSION: The current practice with uniform milligram/kilogram doses leads to highly variable exposures in children due to the non-linear relationship between body weight and alemtuzumab PK. This model may be used for individualized dosing of alemtuzumab.

Originele taal-2Engels
Pagina's (van-tot)1609-1620
Aantal pagina's12
TijdschriftClinical Pharmacokinetics
Volume58
Nummer van het tijdschrift12
DOI's
StatusGepubliceerd - dec. 2019
Extern gepubliceerdJa

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