Tang-Liu D D, Williams R L, Riegelman S
J Pharmacol Exp Ther. 1983 Jan;224(1):180-5.
The disposition of caffeine and its metabolites was studied in six healthy subjects by use of sensitive and specific assays. The primary degradation of caffeine in man was found to be N-demethylation and/or ring oxidation to theophylline, paraxanthine, theobromine and 1,3,7-trimethyluric acid. These compounds were further degraded to dimethylated uric acids, monomethylxanthines and monomethyluric acids. About 3 and 6% of the drug was converted to theophylline and theobromine, respectively. The elimination of paraxanthine after its formation did not follow linear kinetics. A large urine recovery of 1-methylxanthine after caffeine administration in comparison with the amount recovered after administration of theophylline suggests an inhibitory effect on the degradation of this metabolite by either caffeine itself or another metabolite of caffeine. Caffeine and its primary metabolites, dimethylxanthines, were extensively reabsorbed in the renal tubule. Their renal clearances were highly urine flow-dependent and their urinary excretion varied with urine output during the study. About 70% of the dose was recovered in the urine. Postulated degradation pathways of caffeine are discussed.
通过使用灵敏且特异的检测方法，在六名健康受试者中研究了咖啡因及其代谢物的处置情况。发现咖啡因在人体内的主要降解途径是N-去甲基化和/或环氧化生成茶碱、副黄嘌呤、可可碱和1,3,7-三甲基尿酸。这些化合物进一步降解为二甲基尿酸、单甲基黄嘌呤和单甲基尿酸。分别约有3%和6%的药物转化为茶碱和可可碱。副黄嘌呤形成后的消除不遵循线性动力学。与茶碱给药后回收的量相比，咖啡因给药后1-甲基黄嘌呤在尿液中的回收率较高，这表明咖啡因本身或咖啡因的另一种代谢物对该代谢物的降解具有抑制作用。咖啡因及其主要代谢物二甲基黄嘌呤在肾小管中被大量重吸收。它们的肾清除率高度依赖于尿流，并且在研究期间它们的尿排泄量随尿量而变化。约70%的剂量在尿液中回收。文中讨论了推测的咖啡因降解途径。
