PHARMACOKINETICS OF 10-ETHYL-10-DEAZA-AMINOPTERIN, EDATREXATE, GIVEN WEEKLY FOR NON-SMALL-CELL LUNG-CANCER

被引:4
作者
HARTLEY, JM [1 ]
NICHOLSON, PW [1 ]
ALLEN, R [1 ]
LAMOND, P [1 ]
HARLAND, SJ [1 ]
SOUHAMI, RL [1 ]
机构
[1] UCL, SCH MED, DEPT ONCOL, 91 RIDING HOUSE ST, LONDON W1P 8BT, ENGLAND
关键词
D O I
10.1007/BF00685680
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We studied the pharmacokinetics of 10-ethyl-10-deaza-aminopterin (10-EdAM), edatrexate and its 7-hydroxy metabolite during a phase II trial of treatment in advanced non-small-cell lung cancer. A dose of 80 Mg/M2 was given weekly, with dose reduction being undertaken for mucositis or haematological toxicity. A triphasic pattern of plasma elimination was seen, the mean half-lives being 0. 10 +/- 0.07, 0.8 +/- 0.3 and 7 +/- 7 h, respectively. The mean plasma clearance was 25 +/- 14 l/h, with 18 % +/- 11 % of the dose appearing unchanged in the urine. The serum concentration at 1 h accurately predicted the area under the curve (AUC) with r2 = 0.976. There was considerable variation of the clearance both within and between patients but there was no evidence of a dependence on time or dose. The 1-h concentration of the drug was shown to be related to the incidence of toxicity requiring dose reduction. The change in WBC due to the initial dose was shown to be related to both the AUC of the drug and that of its 7-OH metabolite.
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页码:328 / 332
页数:5
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