Development of a pharmacokinetic-guided dose individualization strategy for hydroxyurea treatment in children with sickle cell anaemia.

ABSTRACT:

Aims

Hydroxyurea has emerged as the primary disease-modifying therapy for patients with sickle cell anaemia (SCA). The laboratory and clinical benefits of hydroxyurea are optimal at maximum tolerated dose (MTD), but the current empirical dose escalation process often takes up to 12 months. The purpose of this study was to develop a pharmacokinetic-guided dosing strategy to reduce the time required to reach hydroxyurea MTD in children with SCA.

Methods

Pharmacokinetic (PK) data from the HUSTLE trial (NCT00305175) were used to develop a population PK model using non-linear mixed effects modelling (nonmem 7.2). A D-optimal sampling strategy was developed to estimate individual PK and hydroxyurea exposure (area under the concentration-time curve (AUC)). The initial AUC target wa

SUBMITTER: Dong M 

PROVIDER: S-EPMC4799926 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature