Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer.
Pharmacodynamic and pharmacokinetic study of oral Curcuma extract in patients with colorectal cancer.
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发表时间：
2001-07
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通讯作者：
Ricky A. Sharma;Heather R. McLelland;Kirsti A. Hill;C. Ireson;Stephanie A. Euden;M. Manson;M. Pirmohamed;L. Marnett;A. Gescher;W. Steward
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作者：
Ricky A. Sharma;Heather R. McLelland;Kirsti A. Hill;C. Ireson;Stephanie A. Euden;M. Manson;M. Pirmohamed;L. Marnett;A. Gescher;W. Steward
姜黄属提取物，特别是膳食多酚姜黄素，预防啮齿动物的结肠癌。鉴于姜黄素在人体中的药效学和药代动力学的信息很少，以440至2200 mg/天的剂量进行了一项专有胶囊形式的新型标准化姜黄提取物的剂量递增初步研究，其中含有36-180 mg姜黄素。15例标准化疗难治性晚期结直肠癌患者每天接受姜黄提取物长达4个月。在患者的血细胞中测定谷胱甘肽S-转移酶的活性和由脂质过氧化和前列腺素生物合成的产物丙二醛形成的DNA加合物（M（1）G）的水平。口服姜黄提取物耐受性良好，未观察到剂量限制性毒性。在血液或尿液中均未检测到姜黄素及其代谢产物，但从粪便中回收了姜黄素。在一名患者的粪便中发现了硫酸姜黄素。摄入440毫克姜黄提取物29天，伴随着淋巴细胞谷胱甘肽S-转移酶活性下降59%。在较高剂量水平下，未观察到该效应。每例患者的白细胞M（1）G水平恒定，不受治疗影响。5名患者在2-4个月的治疗中表现出放射学稳定的疾病。结果表明，（a）姜黄提取物可以安全地以每天高达2.2 g的剂量给予患者，相当于180 mg姜黄素;（B）姜黄素在人体内的口服生物利用度低，并且可能经历肠道代谢;以及（c）值得进行姜黄提取物的更大临床试验。
Curcuma spp. extracts, particularly the dietary polyphenol curcumin, prevent colon cancer in rodents. In view of the sparse information on the pharmacodynamics and pharmacokinetics of curcumin in humans, a dose-escalation pilot study of a novel standardized Curcuma extract in proprietary capsule form was performed at doses between 440 and 2200 mg/day, containing 36-180 mg of curcumin. Fifteen patients with advanced colorectal cancer refractory to standard chemotherapies received Curcuma extract daily for up to 4 months. Activity of glutathione S-transferase and levels of a DNA adduct (M(1)G) formed by malondialdehyde, a product of lipid peroxidation and prostaglandin biosynthesis, were measured in patients' blood cells. Oral Curcuma extract was well tolerated, and dose-limiting toxicity was not observed. Neither curcumin nor its metabolites were detected in blood or urine, but curcumin was recovered from feces. Curcumin sulfate was identified in the feces of one patient. Ingestion of 440 mg of Curcuma extract for 29 days was accompanied by a 59% decrease in lymphocytic glutathione S-transferase activity. At higher dose levels, this effect was not observed. Leukocytic M(1)G levels were constant within each patient and unaffected by treatment. Radiologically stable disease was demonstrated in five patients for 2-4 months of treatment. The results suggest that (a) Curcuma extract can be administered safely to patients at doses of up to 2.2 g daily, equivalent to 180 mg of curcumin; (b) curcumin has low oral bioavailability in humans and may undergo intestinal metabolism; and (c) larger clinical trials of Curcuma extract are merited.