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细胞毒性药物对β-乙酰地高辛血药浓度及肾排泄的影响。

Effects of cytostatic drugs on plasma level and renal excretion of beta-acetyldigoxin.

作者信息

Kuhlmann J, Zilly W, Wilke J

出版信息

Clin Pharmacol Ther. 1981 Oct;30(4):518-27. doi: 10.1038/clpt.1981.197.

Abstract

Mucosal defects decrease digoxin absorption in patients with malabsorption syndromes. Since the intestinal mucosa can be damaged by cytostatic drugs, we investigated their effects on digoxin plasma levels and urinary digoxin excretion. In six patients with malignant lymphoma who received 0.8 mg beta-acetyldigoxin before and 24 hr after treatment with a combination of cyclophosphamide, oncovin, procarbazine, and prednisone (COPP) or cyclophosphamide, oncovin, and prednisone (COP), plasma digoxin concentrations were measured 0 to 8 hr after the dose and areas under the plasma concentration-time curves were calculated. In 15 patients on 0.3 mg of beta-acetyldigoxin daily, plasma glycoside concentrations and renal excretion were measured daily before and after COPP, COP, cyclophosphamide, oncovin, cytosine-arabinosine, and prednisone (COAP), or adriamycin, bleomycin, and prednisone (ABP) treatment schemes. The diminished steady-state glycoside plasma concentrations and daily renal glycoside excretion during the 24 to 168 hr after the cytostatic drug established reversible impairment of digoxin absorption. The delayed time to peak after a single dose of digoxin during cytostatic drug therapy shows that extent and rate of digoxin absorption are reduced. To maintain adequate control of digoxin therapy in patients treated with cytostatic drugs, plasma levels should be monitored.

摘要

黏膜缺损会降低吸收不良综合征患者地高辛的吸收。由于细胞毒性药物可损伤肠黏膜,我们研究了它们对地高辛血药浓度及尿地高辛排泄的影响。6例恶性淋巴瘤患者在接受环磷酰胺、长春新碱、丙卡巴肼和泼尼松(COPP)或环磷酰胺、长春新碱和泼尼松(COP)联合治疗前及治疗24小时后服用0.8毫克β-乙酰地高辛,给药后0至8小时测量地高辛血药浓度,并计算血药浓度-时间曲线下面积。15例每日服用0.3毫克β-乙酰地高辛的患者,在接受COPP、COP、环磷酰胺、长春新碱、阿糖胞苷和泼尼松(COAP)或阿霉素、博来霉素和泼尼松(ABP)治疗方案前后,每日测量血药糖苷浓度和肾脏排泄情况。细胞毒性药物治疗后24至168小时内,稳态血药糖苷浓度降低及每日肾脏糖苷排泄减少,表明地高辛吸收出现可逆性损害。细胞毒性药物治疗期间,单次服用地高辛后达峰时间延迟,表明地高辛吸收程度和速率降低。为了在用细胞毒性药物治疗的患者中维持地高辛治疗的充分控制,应监测血药浓度。

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