A URINARY METABOLITE RATIO THAT REFLECTS SYSTEMIC CAFFEINE CLEARANCE
A URINARY METABOLITE RATIO THAT REFLECTS SYSTEMIC CAFFEINE CLEARANCE
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DOI：
10.1038/clpt.1987.126
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发表时间：
1987-08-01
影响因子：
6.7
通讯作者：
KALOW, W
中科院分区：
文献类型：
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作者：
CAMPBELL, ME;SPIELBERG, SP;KALOW, W
对15名有不同细胞色素P-450诱导剂(香烟烟雾)和抑制剂(口服避孕药)暴露史的受试者进行了全身咖啡因清除和尿代谢物分析。根据对黄嘌呤7-脱甲基化产物相对于对黄嘌呤8-羟基化产物的摩尔回收率，观察到咖啡因清除量与尿率之间存在相关性(r=0.91P<；0.001)。在更大的人群中进行了尿代谢物分析，以评估性别、年龄、口腔、避孕药和吸烟对这一比例的影响。成人和儿童之间没有性别差异；儿童(n=21)的平均代谢物比率(P<；0.001)高于成人(n=61)，口服避孕药(n=9)的比率低于不服用口服避孕药的妇女(n=30)，吸烟者(n=26)的比率(P<；0.001)高于不吸烟者(n=61)。这些数据表明，基于对黄嘌呤7-去甲基化/8-羟基化产物的尿代谢物比率反映了全身咖啡因的清除，并可能监测多环芳烃诱导的细胞色素P-450活性。
Systemic caffeine clearance and urinary metabolite profiles were determined in 15 subjects with diverse exposure histories to cytochrome P-450 inducers (cigarette smoke) and inhibitors (oral contraceptive steroids). A correlation was observed between caffeine clearance and a urinary ratio based on the molar recovery of paraxanthine 7-demthylation products relative to a paraxanthine 8-hydroxylation product (r = 0.91; P < 0.001). Analysis of urinary metabolites was undertaken in a larger population to assess the effects of gender, age, oral, contraceptives, and smoking on the ratio. No gender differences were observed in either adults or children; children (n = 21) showed a higher (P < 0.001) mean metabolite ratio than adults (n = 61), oral contraceptive users (n = 9) had lower (P < 0.05) ratios than women not taking oral contraceptives (n = 30), and smokers (n = 26) had higher (P < 0.001) ratios than nonsmokers (n = 61). The data indicate that a urinary metabolite ratio based on paraxanthine 7-demethylation/8-hydroxylation products reflects systemic caffeine clearance and likely monitors cytochrome P-450 activity inducible by polycyclic aromatic hydrocarbons.