Lu X H, Yin L J
Affiliated Hospital of Shan dong Medical University, Jinan.
Zhonghua Fu Chan Ke Za Zhi. 1994 Dec;29(12):729-31, 762.
The platinum-containing compounds has become a major chemical agent in the treatment of cancer. A circadian rhythm in the susceptibility of rodents and human being to cisplatin has been demonstrated, the maximal tolerance being found in the animal's active phase. Carboplatin is a second generation analog. Two studies were performed on mice with carboplatin under 12:12 light dark cycle to study its chronotoxicity and chronoeffectiveness. In study I, single intraperitoneal injection of 192mg/kg (LD50) carboplatin was given to four groups of mice at four different circadian stage. It was found that at 50% the overall mortality of mice, there was a mortality difference of 28% for mice receiving the drug at 9 a.m. to 71% for mice receiving drug at 9 p.m. It demonstrated that carboplatin was better tolerated in the animal's early sleep phase. In study II, S180 tumor-bearing mice were treated with 50mg/kg of carboplatin. The longest mean survival time and the lowest marrow toxicity occurred in the group which received the drug at the beginning of the sleep phase. It showed that the susceptibility of mice to carboplatin is circadian stage dependent. These data clearly demonstrate that, by timing the administration of drugs according to body rhythms, such as the host susceptibility-resistance rhythm to a drug, one can gain a therapeutic advantage over an approach which ignores such rhythms.
含铂化合物已成为癌症治疗中的主要化学药剂。啮齿动物和人类对顺铂的易感性存在昼夜节律，在动物的活跃期耐受性最强。卡铂是第二代类似物。在12:12明暗周期下，对小鼠进行了两项关于卡铂的研究，以研究其时辰毒性和时辰疗效。在研究I中，将192mg/kg（半数致死量）的卡铂腹腔注射给四组小鼠，给药时间分别处于四个不同的昼夜阶段。结果发现，在小鼠总体死亡率为50%时，上午9点给药的小鼠死亡率差异为28%，而晚上9点给药的小鼠死亡率差异为71%。这表明卡铂在动物的早期睡眠阶段耐受性更好。在研究II中，用50mg/kg的卡铂治疗荷S180肿瘤小鼠。在睡眠阶段开始时给药的组中，平均生存时间最长且骨髓毒性最低。这表明小鼠对卡铂的易感性取决于昼夜阶段。这些数据清楚地表明，根据身体节律（如宿主对药物的易感性-抗性节律）来安排给药时间，相对于忽视这些节律的给药方式，可以获得治疗优势。
