We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Pharmacogenetics of Intravenous and Oral Busulfan in Hematopoietic Cell Transplant Recipients.
- Authors
Abbasi, Nissa; Vadnais, Barbara; Knutson, Jennifer A.; Blough, David K.; Kelly, Edward J.; O’Donnell, Paul V.; Deeg, H.Joachim; Pawlikowski, Matthew A.; Ho, Rodney J.-Y.; McCune, Jeannine S.
- Abstract
Kinetics-based dose targeting is often conducted in hematopoietic cell transplant (HCT) patients conditioned with intravenous (IV) or oral busulfan to lower rates of rejection, nonrelapse mortality, and relapse. Using the candidate gene approach, the authors evaluated whether busulfan clearance was associated with polymorphisms in the genes regulating the predominant metabolizing enzymes involved in busulfan conjugation, specifically glutathione S-transferase (GST) isoenzymes A1 (GSTA1) and M1 (GSTM1). Busulfan clearance was estimated after the morning dose on days 1, 2, and 3; each patient’s average clearance was used for analyses. The average (± standard deviation) busulfan clearance was 3.2 ± 0.56 mL/min/kg in the separate population of 95 patients who received oral busulfan and 103 ± 24 ml/min/m2 in the 57 patients who received IV busulfan. Oral busulfan clearance was associated with GSTA1 (P = .008) but not GSTM1 (P = .57) genotypes. However, among the GSTA1 haplotypes (ie, *A*A, *A*B, *B*B), there was significant overlap in the observed oral busulfan clearance and similar rates of achieving the target busulfan exposure. Clearance of IV busulfan was not associated with GSTA1 (P = .21) or GSTM1 (P = .99). These data suggest that personalizing either IV or oral busulfan dosing cannot be simplified on the basis of GSTA1 or GSTM1 genotype.
- Subjects
ANALYSIS of variance; ANTINEOPLASTIC agents; BIOLOGICAL assay; BIOTRANSFORMATION (Metabolism); CHI-squared test; DRUG monitoring; GAS chromatography; GENES; GENETIC polymorphisms; HEMATOPOIETIC stem cell transplantation; INTRAVENOUS therapy; LENNOX-Gastaut syndrome; LONGITUDINAL method; MASS spectrometry; ORAL drug administration; HEALTH outcome assessment; PHARMACEUTICAL arithmetic; POLYMERASE chain reaction; REGRESSION analysis; RESEARCH funding; SPECTROPHOTOMETRY; STATISTICAL power analysis; TREATMENT effectiveness; RETROSPECTIVE studies; PATIENT-centered care; DATA analysis software
- Publication
Journal of Clinical Pharmacology, 2011, Vol 51, Issue 10, p1429
- ISSN
0091-2700
- Publication type
Article
- DOI
10.1177/0091270010382915