INTRACELLULAR PHARMACOKINETICS OF 2-CHLORODEOXYADENOSINE IN LEUKEMIA-CELLS FROM PATIENTS WITH CHRONIC LYMPHOCYTIC-LEUKEMIA

被引:0
|
作者
ALESSISEVERINI, S
GATI, WP
BELCH, AR
PATERSON, ARP
机构
[1] UNIV ALBERTA, DEPT PHARMACOL, EDMONTON, AB T6G 2H7, CANADA
[2] CROSS CANC INST, DEPT MED, EDMONTON, AB T6G 1Z2, CANADA
关键词
2-CHLORODEOXYADENOSINE (2-CDA); NITROBENZYLTHIOINOSINE (NBMPR); CHRONIC LYMPHOCYTIC LEUKEMIA (CLL); NUCLEOSIDE TRANSPORT INHIBITION; TRANSPORTER-MEDIATED EFFLUX; EFFLUX BLOCKADE;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
2-Chlorodeoxyadenosine (2-CdA) is an important agent in the treatment of hairy cell leukemia and chronic lymphocytic leukemia (CLL). Others have reported that levels of 2-CdA phosphates present in human leukemia cells decline rapidly when the cells are in 2-CdA-free medium (Santana et al. J Clin Oncol 1991; 9: 416-422). In the present study, time-courses of 2-CdA lass from CLL cells were biexponential: the mean half-life of the initial phase was 0.30 +/- 0.18 h; the presence of 0.5 mu M nitrobenzylthioinosine (NBMPR, a classical inhibitor of nucleoside transport) in the suspending medium, significantly decreased the initial rate of 2-CdA efflux (mean half-life, 0.43 +/- 0.22 h). As a consequence, AUCs (areas under time-course plots) were significantly higher in the NBMPR-treated cells (4.56 +/- 2.01 pmol . h/10(6) cells, n = 19) than in untreated control cells (3.83 +/- 1.74 pmol . h/10(6) cells; n = 19). 2-CdA was the principal efflux product released into the medium from 2-CdA-loaded CLL cells. We conclude that nucleoside transport processes contribute to the efflux of 2-CdA from CLL cells and that NBMPR may be useful as a retentive agent.
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页码:1674 / 1679
页数:6
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