Zidovudine pharmacokinetics in zidovudine-induced bone marrow toxicity

Barry, M., Howe, J.L., Back, D.J., Swart, A.M., Breckenridge, A.M., Weller, I.V.D., Beeching, N. and Nye, F. (1994) Zidovudine pharmacokinetics in zidovudine-induced bone marrow toxicity. British Journal of Clinical Pharmacology, 37 (1). pp. 7-12. ISSN 0306-5251

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Abstract

1 The major adverse effect of zidovudine (ZDV) is haematological toxicity which results in anaemia and granulocytopenia. The aim of the present study was to investigate if HIV-positive patients developing erythroid aplasia/hypoplasia are exposed to higher plasma concentrations of ZDV owing to impaired hepatic metabolism to the major metabolite, 3'-azido-3'-deoxy- 5'-ß-D-glucopyranurosonylthymidine (GZDV). 2 Twelve HIV-positive male patients were studied, six having developed bone marrow aplasia/hypoplasia within the first 6 months of ZDV therapy. Each of the patients exhibiting toxicity were matched for age, weight, risk factors for HIV infection and disease stage with patients who had no evidence of early bone marrow toxicity. 3 ZDV was administered orally in doses of 3-10 mg kg and blood samples taken at intervals to 6 h. Urine was collected over the whole 6 h period. ZDV and GZDV were assayed by h.p.l.c. 4 There were no significant differences in the pharmacokinetic parameters between the two groups of patients. For patients with early bone marrow toxicity the elimination half- life of ZDV was 1.10 ± 0.16 h with an oral clearance of 2752 ± 1031 ml min compared with values of 1.06 ± 0.18 h and 2843 ± 730 ml min seen in the control group. Similarly there was no significant difference in the pharmacokinetics of GZDV or the urinary ratio of GZDV to ZDV. 5 Therefore, despite the fact that ZDV toxicity to haematopoietic progenitor cells has been previously shown to be dose related, there was no indication from this study that it is directly related to plasma concentrations of ZDV.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: Pure Connector
Date Deposited: 24 Sep 2013 00:56
Last Modified: 21 Apr 2020 21:54
URI: https://ueaeprints.uea.ac.uk/id/eprint/43397
DOI: 10.1111/j.1365-2125.1994.tb04231.x

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