Glutathione Transferase Gene Variants Influence Busulfan Pharmacokinetics and Outcome After Myeloablative Conditioning.

ABSTRACT:

Background

Busulfan (Bu) and cyclophosphamide (Cy) are frequently included in conditioning regimens before hematopoietic stem cell transplantation (HSCT). Both drugs are detoxified by glutathione transferases (GST), and GST gene variants may explain some of the interindividual variability in pharmacokinetics and drug toxicity.

Methods

The study investigated adult patients (n = 114) receiving oral Bu pre-HSCT. Bu doses were adjusted to obtain an average steady-state concentration (Css) of 900 mcg/L.

Results

Median first dose Bu Css was 1000 mcg/L (600-1780 mcg/L). Patients carrying 1 and 2 GSTA1*B (rs3957357) alleles demonstrated median 12% and 16% higher Bu Css (P ≤ 0.05). Bu exposure (average Css; odds ratio = 1.009, 95% confidence interval = 1.002-1.017, P = 0.013)

SUBMITTER: Bremer S 

PROVIDER: S-EPMC4505914 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature