Cyclophosphamide pharmacokinetics and pharmacogenetics in children with B-cell non-Hodgkin's lymphoma

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
Gareth J VealAlan V Boddy

Abstract

Variation in cyclophosphamide pharmacokinetics and metabolism has been highlighted as a factor that may impact on clinical outcome in various tumour types. The current study in children with B-cell non-Hodgkin's lymphoma (NHL) was designed to corroborate previous findings in a large prospective study incorporating genotype for common polymorphisms known to influence cyclophosphamide pharmacology. A total of 644 plasma samples collected over a 5 year period, from 49 B-cell NHL patients ≤ 18 years receiving cyclophosphamide (250 mg/m(2)), were used to characterise a population pharmacokinetic model. Polymorphisms in genes including CYP2B6 and CYP2C19 were analysed. A two-compartment model provided the best fit of the population analysis. The mean cyclophosphamide clearance value following dose 1 was significantly lower than following dose 5 (1.83 ± 1.07 versus 3.68 ± 1.43 L/h/m(2), respectively; mean ± standard deviation from empirical Bayes estimates; P < 0.001). The presence of at least one CYP2B6*6 variant allele was associated with a lower cyclophosphamide clearance following both dose 1 (1.54 ± 0.11 L/h/m(2) versus 2.20 ± 0.31 L/h/m(2), P = 0.033) and dose 5 (3.12 ± 0.17 L/h/m(2) versus 4.35 ± 0.37 L/h/m(2), P = 0.0028), as ...Continue Reading

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Citations

Sep 13, 2016·International Journal of Molecular Sciences·Vid MlakarMarc Ansari
Sep 20, 2016·Clinical Pharmacokinetics·Daphne BertholeeAndré B P van Kuilenburg
Apr 11, 2017·Drug Metabolism Reviews·Ivanna HrynchakVera Marisa Costa
Jan 14, 2017·Journal of Clinical Pharmacology·Francine Attié de CastroVera Lucia Lanchote
Feb 9, 2019·Acta Ophthalmologica·Sanne E DetigerDion Paridaens
May 15, 2018·Clinical Pharmacology and Therapeutics·Evan D Kharasch, Amanda Crafford
Jan 4, 2017·Expert Opinion on Pharmacotherapy·G Moroni, C Ponticelli
Dec 5, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Olivia CampagneClinton F Stewart
Jun 12, 2021·Cancer Chemotherapy and Pharmacology·Nuala HelsbyDavid Porter
Jun 28, 2021·Pharmacology & Therapeutics·Daniele LavacchiStefania Nobili

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Methods Mentioned

BETA
genotyping
PCR

Software Mentioned

NONMEM
GraphPad
GraphPad Prism
SPSS

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