Chan Siu-Lung, Yeung John H K
Department of Pharmacology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China.
Food Chem Toxicol. 2006 Sep;44(9):1607-12. doi: 10.1016/j.fct.2006.03.008. Epub 2006 Apr 25.
Polysaccharide peptide (PSP), isolated from Coriolus versicolor COV-1, has been previously shown to have immuno-stimulatory, anti-tumour and analgesic effects in animal models. When used as an adjunct in cancer chemotherapy in clinical trials carried out in China, PSP improved the quality of life in the patients by improving appetite and alleviating symptoms associated with cancer chemotherapy. In this study, the effects of non-toxic doses of PSP on phase I metabolism was investigated in the rat, using the conventional probe antipyrine. Acute PSP (3-5 micromol/kg, i.p.) treatment did not produce significant changes in antipyrine clearance. Sub-chronic treatment with PSP (1-3 micromol/kg/day, i.p., 3 days) decreased the antipyrine clearance (30-35%), with an increase in the plasma half-life (T1/2) by 55% and an increase in the area under concentration-time curve (AUC) by 61%. Total hepatic cytochrome P450 (P450) was dose-dependently decreased (32-54%) after sub-chronic, but not the acute treatment of PSP. Given that PSP can affect phase I metabolism and hepatic cytochrome P450 content, the concomitant use of PSP with other therapeutic agents that undergo phase I metabolism should be carefully monitored.
云芝多糖肽(PSP)是从云芝COV-1中分离得到的,此前已证明其在动物模型中具有免疫刺激、抗肿瘤和镇痛作用。在中国进行的临床试验中,PSP作为癌症化疗的辅助药物使用时,通过改善食欲和减轻与癌症化疗相关的症状,提高了患者的生活质量。在本研究中,使用传统的探针安替比林,研究了无毒剂量的PSP对大鼠I期代谢的影响。急性给予PSP(3-5微摩尔/千克,腹腔注射)对安替比林清除率没有显著影响。亚慢性给予PSP(1-3微摩尔/千克/天,腹腔注射,3天)可降低安替比林清除率(30-35%),使血浆半衰期(T1/2)增加55%,浓度-时间曲线下面积(AUC)增加61%。亚慢性而非急性给予PSP后,肝脏总细胞色素P450(P450)呈剂量依赖性降低(32-54%)。鉴于PSP可影响I期代谢和肝细胞色素P450含量,在同时使用PSP与其他进行I期代谢的治疗药物时应谨慎监测。