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[腹腔内或口服依托泊苷在动物体内的抗肿瘤活性及其给药方案依赖性]

[The antitumor activity of intraperitoneally- or orally-administered etoposide in animals and its administration-schedule dependency].

作者信息

Okamoto K, Nishikawa K, Seki T, Shibasaki C, Uchida T, Takahashi K

出版信息

Gan To Kagaku Ryoho. 1985 Dec;12(12):2331-7.

PMID:4073928
Abstract

The antitumor activity of etoposide against a wide variety of transplantable tumors in mice and rats was examined. Etoposide exhibited antitumor activity by both i.p. and p.o. administrations but a much larger effect was obtained in the former case. In addition, the effective dose of etoposide was much less in i.p. administration. In order to further investigate this large difference of etoposide effect the level of etoposide in the blood was followed after administration of 3H-etoposide via i.p. and p.o. routes. Although the maximum levels for both were seen 10 to 20 min after administration, the level in i.p. administration was much higher than that in p.o. administration. For instance, the level seen for i.p. administration at 8 mg/kg was comparable to that for p.o. administration at a much higher dose of 128 mg/kg. The administration schedule dependency of etoposide antitumor activity was examined using L1210 leukemia as the target tumor. When etoposide was administered alone on day, 1, the effect was the smallest obtained in i.p. as well as in p.o. administrations among the schedules examined in this study. Under other schedules where etoposide was administered i.p. and p.o. once a day for 3, 5 and 9 consecutive days from day 1 and on every other day, that is, days 1, 3 and 5, higher antitumor effects were seen.

摘要

对依托泊苷针对小鼠和大鼠多种可移植肿瘤的抗肿瘤活性进行了研究。依托泊苷通过腹腔注射和口服给药均表现出抗肿瘤活性,但在前一种情况下效果要大得多。此外,依托泊苷腹腔注射的有效剂量要少得多。为了进一步研究依托泊苷效果的这种巨大差异,在通过腹腔注射和口服途径给予³H-依托泊苷后,追踪血液中依托泊苷的水平。尽管两者在给药后10至20分钟均达到最高水平,但腹腔注射的水平远高于口服给药的水平。例如,腹腔注射8mg/kg时的水平与口服128mg/kg更高剂量时的水平相当。以L1210白血病作为靶肿瘤,研究了依托泊苷抗肿瘤活性的给药方案依赖性。当在第1天单独给予依托泊苷时,在本研究中所检测的给药方案中,腹腔注射和口服给药的效果均最小。在其他给药方案中,从第1天开始连续3天、5天和9天每天一次腹腔注射和口服依托泊苷,以及隔天给药,即第1天、第3天和第5天给药时,观察到更高的抗肿瘤效果。

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