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[晚期胃癌癌性腹膜炎患者腹腔输注顺铂加或不加硫代硫酸钠解救后的药代动力学]

[Pharmacokinetics following intraperitoneal infusion of cisplatinum with and without sodium thiosulfate rescue in carcinomatous peritonitis in advanced gastric cancers].

作者信息

Namatame K, Kou Y, Nakayoshi A

机构信息

Dept. of Surgery, Showa University Fujigaoka Hospital.

出版信息

Gan To Kagaku Ryoho. 1991 Aug;18(11):1784-9.

PMID:1877818
Abstract

The pharmacokinetics of ip cisplatinum (100 mg/body) was studied in 10 patients with advanced gastric cancer. Five patients were administered ip-cisplatinum with STS and another 5 patients were given the same without STS. As a result, 1) the level of free-CDDP in ascites fluid was significantly elevated after administration, showing that free-CDDP possessing anti-tumor activity persisted in the ascites fluid for a long time and reached the peak concentration 30 minutes after administration. 2) The free-CDDP transferred into the blood after administration also persisted for a long time in parallel with changes in the free-CDDP level in the ascites fluid. 3) The AUC, MRT and VRT of the free-CDDP concentration in the peritoneal cavity after ip administration of CDDP were high, clearly indicating the direct effect on peritoneal concentration. 4) The AUC, MRT and VRT of free-CDDP in the venous phase after ip administration of CDDP were higher than after its iv administration, suggesting that effects equivalent to or greater than those of the iv route drug can be expected in the venous phase. 5) The frequency of side effects induced by the combination of STS was lower than that of side effects induced by the administration without combined STS. Much larger doses of CDDP may be given ip by combining with STS.

摘要

对10例晚期胃癌患者研究了腹腔注射顺铂(100mg/体)的药代动力学。5例患者腹腔注射顺铂联合丝裂霉素,另外5例患者腹腔注射顺铂但不联合丝裂霉素。结果显示:1)给药后腹水中游离顺铂水平显著升高,表明具有抗肿瘤活性的游离顺铂在腹水中长时间持续存在,并在给药后30分钟达到峰值浓度。2)给药后转移到血液中的游离顺铂也与腹水中游离顺铂水平的变化平行,长时间持续存在。3)腹腔注射顺铂后,腹腔内游离顺铂浓度的AUC、MRT和VRT较高,清楚地表明对腹腔浓度有直接影响。4)腹腔注射顺铂后静脉期游离顺铂的AUC、MRT和VRT高于静脉注射后,表明在静脉期可预期达到等同于或大于静脉给药途径药物的效果。5)丝裂霉素联合用药引起的副作用发生率低于不联合用药时的副作用发生率。联合丝裂霉素腹腔注射时,可给予大得多剂量的顺铂。

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1
[Pharmacokinetics following intraperitoneal infusion of cisplatinum with and without sodium thiosulfate rescue in carcinomatous peritonitis in advanced gastric cancers].[晚期胃癌癌性腹膜炎患者腹腔输注顺铂加或不加硫代硫酸钠解救后的药代动力学]
Gan To Kagaku Ryoho. 1991 Aug;18(11):1784-9.
2
[Intraperitoneal (Ip) administration of cisplatin in combination with systemic chemotherapy in patients with malignant ascites of gastrointestinal cancer: clinical evaluation and pharmacokinetics].[顺铂腹腔内(Ip)给药联合全身化疗治疗胃肠道癌恶性腹水的临床评估及药代动力学]
Gan No Rinsho. 1988 Feb;34(2):191-5.
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[Intraperitoneal high-dose cisplatinum chemotherapy (CDDP-ip) in patients with carcinomatous peritonitis].
Gan To Kagaku Ryoho. 1987 Apr;14(4):1025-32.
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[Intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers].
Gan To Kagaku Ryoho. 1993 Aug;20(11):1645-8.
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[Pharmacokinetic study of cisplatin and sodium thiosulfate in two-route-infusion chemotherapy].顺铂与硫代硫酸钠两途径输注化疗的药代动力学研究
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[Studies on an appropriate intra thoracic administration of cisplatin and sodium thiosulfate in malignant pleural effusion].[顺铂与硫代硫酸钠胸腔内给药治疗恶性胸腔积液的适宜剂量研究]
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8
[Clinical efficacy of two-route chemotherapy with CDDP and STS in patients with peritonitis carcinomatosa].
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[Effect of cisplatin (CDDP) against peritonitis carcinomatosa in nude mice inoculated intraperitoneally with human gastric cancer].
Gan To Kagaku Ryoho. 1985 Aug;12(8):1638-43.