Lelo A, Miners J O, Robson R A, Birkett D J
Br J Clin Pharmacol. 1986 Aug;22(2):183-6. doi: 10.1111/j.1365-2125.1986.tb05247.x.
Five subjects who participated in an earlier study (Lelo et al., 1986b) of the comparative pharmacokinetics of caffeine (CA) and its primary monodemethylated metabolites paraxanthine (PX), theobromine (TB) and theophylline (TP) were administered CA to steady-state. Using areas under the plasma concentration-time curves for each of the dimethylxanthines derived from CA in the steady-state study and individual plasma clearances of PX, TB and TP determined in the previous study, the fractional conversion of CA to PX, TB and TP and the individual partial clearances of CA have been defined. The mean (+/- s.d.) fractional conversion of CA to PX, TB and TP was 79.6 +/- 21.0%, 10.8 +/- 2.4% and 3.7 +/- 1.3%, respectively. When only demethylation pathways are considered PX, TB and TP accounted for 83.9 +/- 5.4%, 12.1 +/- 4.1% and 4.0 +/- 1.4%, respectively of the CA demethylations. The mean partial clearance of CA to PX was approximately 8-fold and 23-fold greater than those to TB and TP respectively. These data confirm earlier reports that PX is the major metabolite of CA in humans but suggest that PX formation is quantitatively more important than previously believed.
五名参与了一项关于咖啡因（CA）及其主要单去甲基化代谢产物对黄嘌呤（PX）、可可碱（TB）和茶碱（TP）比较药代动力学的早期研究（Lelo等人，1986b）的受试者被给予CA直至达到稳态。利用稳态研究中从CA衍生的每种二甲基黄嘌呤的血浆浓度-时间曲线下面积以及先前研究中测定的PX、TB和TP的个体血浆清除率，已定义了CA向PX、TB和TP的分数转化率以及CA的个体部分清除率。CA向PX、TB和TP的平均（±标准差）分数转化率分别为79.6±21.0%、10.8±2.4%和3.7±1.3%。仅考虑去甲基化途径时，PX、TB和TP分别占CA去甲基化的83.9±5.4%、12.1±4.1%和4.0±1.4%。CA向PX的平均部分清除率分别比向TB和TP的平均部分清除率大约高8倍和23倍。这些数据证实了早期的报道，即PX是人类中CA的主要代谢产物，但表明PX的形成在数量上比以前认为的更重要。
