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Cyclophosphamide metabolism in children with Fanconi's anaemia

Lookup NU author(s): Mike Cole, Professor Andrew Pearson, Professor Alan Boddy

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Abstract

Although patients with Fanconi's anaemia (FA) exhibit a heightened sensitivity to DNA cross-linking agents, modified doses of CY continue to be used in their conditioning prior to BMT. We measured the pharmacokinetics and metabolism of CY in six children with FA using an established high performance thin layer chromatography technique. CY doses ranged between 5 and 20 mg/kg (median 10 mg/kg), The median CY clearance was 0.6 1/h/m(2) (range 0.4-1.1 1/h/m(2)), t(1/2) was 8.1 h (range 6.7-9.5 h) and volume of distribution was 0.19 1/kg (range 0.16-0.34 1/kg), respectively. These results contrast with those previously reported from a comparable group of non-FA children in whom the median CY clearance was 3.2 1/h/m(2) (range 2-5 1/h/m(2)) (P = 0.035), t(1/2) was 2.4 h (range 2-3.8 h) (P = 0.035) and volume of distribution 0.5 1/kg (range 0.26-0.95 1/kg) (NS), Unlike the control group in whom the presence of inactive metabolites of CY was common, metabolites could not be found in any FA patient. The enhanced sensitivity of children with FA to CY may in part result from altered drug metabolism.


Publication metadata

Author(s): Yule, S. M., Price, L., Cole, M., Pearson, A. D. J., Boddy, A. V.

Publication type: Article

Publication status: Published

Journal: Bone Marrow Transplantation

Year: 1999

Volume: 24

Issue: 2

Pages: 123-128

Print publication date: 01/07/1999

ISSN (print): 0268-3369

ISSN (electronic): 1476-5365

URL: http://dx.doi.org/10.1038/sj.bmt.1701868

DOI: 10.1038/sj.bmt.1701868


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