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Phenotypical difference in deamination of cytarabine is not evident in induction therapy for acute myeloid leukaemia
- Source :
- European Journal of Hospital Pharmacy. 20:185-188
- Publication Year :
- 2013
- Publisher :
- BMJ, 2013.
-
Abstract
- Objective To investigate the uracil arabinoside/cytarabine (Ara-U/Ara-C) ratios with the lower dose in adult acute myeloid leukaemia (AML) induction therapy (100 mg/m 2 Ara-C) where no enzyme saturation is expected. Methods A precise and robust high-performance liquid chromatography (HPLC) method for simultaneous determination of Ara-C and its main inactive metabolite Ara-U in human plasma was developed and validated. Nineteen patients with acute myeloid leukaemia were treated with Ara-C in a dose of 100 mg/m 2 together with daunorubicin and etoposide. Plasma concentrations were used to construct the standard normality plot to indicate towards two different phenotypes for the deamination enzyme. This was confirmed with the Shapiro–Wilks test for normality and a histogram of the distribution of the ratios. Results The lower limits of quantification (LLoQ) of the developed method were 32 ng/ml and 10 ng/ml for Ara-C and Ara-U, respectively. Precision, accuracy, recovery, selectivity and stability varied by no more than 15% at concentrations above LLoQ and by 20% at LLoQ, except for long-term stability of Ara-U. Both the Shapiro–Wilks test for normality and the histogram showed a unimodal distribution. The non-transformed values of the Ara-U/Ara-C ratios were between 0.3 and 17.7 (median 2.2). No correlations between Ara-U/Ara-C ratios and age, sex, liver or renal function or treatment outcome were found. Fifteen of the 19 patients had complete remission of the disease and 2 had partial remission. Conclusions Division into slow and fast Ara-C metabolisers in this patient population could not be made and specific dose individualisations can therefore not be recommended.
- Subjects :
- Chemotherapy
medicine.medical_specialty
Daunorubicin
business.industry
medicine.medical_treatment
Metabolite
food and beverages
Renal function
biochemical phenomena, metabolism, and nutrition
High-performance liquid chromatography
Gastroenterology
carbohydrates (lipids)
Normality test
chemistry.chemical_compound
chemistry
Internal medicine
Immunology
medicine
Cytarabine
lipids (amino acids, peptides, and proteins)
heterocyclic compounds
General Pharmacology, Toxicology and Pharmaceutics
business
Etoposide
medicine.drug
Subjects
Details
- ISSN :
- 20479964 and 20479956
- Volume :
- 20
- Database :
- OpenAIRE
- Journal :
- European Journal of Hospital Pharmacy
- Accession number :
- edsair.doi...........d7b5e19b3dc8631f7956be478c8325b7