Role of and Genetic Polymorphisms in Hydroxyurea Pharmacokinetics.

BACKGROUND

Hydroxyurea is approved for the treatment of paediatric and adult sickle cell disease patients. It causes the synthesis of foetal haemoglobin and decreases platelets and granulocytes, but with a high interindividual variability, requiring higher dosages and escalating toxicity. Hereditary variables should be investigated to personalise treatment. We evaluated the possible influences of and gene polymorphisms on hydroxyurea pharmacokinetics.

METHODS

We conducted a retrospective analysis on 79 treated patients. The polymorphisms of (rs683369 G > C) and (rs9376230 C > A and rs9483947 C > T) were genotyped.

RESULTS

Sub-Saharan patients with the rs683369 GG genotype showed a lower drug half-life, compared to those with the GC genotype. In sub-Saharan paediatric female patients, the rs683369 GG genotype was associated with a lower t1/2 than the GC genotype.

CONCLUSIONS

The findings demonstrate for the first time how crucial it is to assess the pharmacogenetics of hydroxyurea by taking into account the two sexes in different groups. Additionally, the data were evaluated with consideration for ethnic groups and individually for adults and children. Pharmacogenetic studies could improve the clinical management of hydroxyurea.