Shin S G, Juan D, Rammohan M
Clinical Research Center, Northwestern Memorial Hospital, Chicago, Ill.
Clin Pharmacol Ther. 1988 Nov;44(5):522-30. doi: 10.1038/clpt.1988.189.
The effect of age on theophylline kinetics was examined in six normal young men and six elderly men. There were no age-associated differences in theophylline volume of distribution, total clearance, or t1/2. The unbound fraction of theophylline was significantly raised in the elderly (mean 77.7% vs. 62.3%, p less than 0.001) and was correlated with the serum albumin level (r = -0.7, p less than 0.01). Theophylline nonrenal clearance was not changed, but the total unbound clearance was significantly reduced in the elderly subjects as compared with the young ones (mean 0.744 vs. 1.085 ml/min/kg, p less than 0.05). Creatinine clearance was reduced in the elderly and was significantly correlated with unbound renal clearance (r = 0.6, p less than 0.04). There were no age-related differences in the urinary excretion of theophylline, 1-methyluric acid, 3-methylxanthine, or 1,3-dimethyluric acid. However, significant reduction in unbound renal theophylline clearance (p less than 0.002) as well as the unbound metabolic clearance of 1,3-dimethyluric acid (p less than 0.03), 3-methylxanthine (p less than 0.04), and 1-methyluric acid (p less than 0.02) were observed in the elderly subjects. These observations indicate that both renal and metabolic elimination processes for theophylline are less active in the normal elderly.
在6名正常年轻男性和6名老年男性中研究了年龄对茶碱动力学的影响。茶碱的分布容积、总清除率或t1/2在年龄上没有差异。老年患者中茶碱的游离分数显著升高（平均77.7%对62.3%，p<0.001），且与血清白蛋白水平相关（r=-0.7，p<0.01）。老年受试者的茶碱非肾清除率没有变化，但总游离清除率与年轻受试者相比显著降低（平均0.744对1.085ml/min/kg，p<0.05）。老年患者的肌酐清除率降低，且与游离肾清除率显著相关（r=0.6，p<0.04）。茶碱、1-甲基尿酸、3-甲基黄嘌呤或1,3-二甲基尿酸的尿排泄在年龄上没有差异。然而，在老年受试者中观察到游离肾茶碱清除率显著降低（p<0.002）以及1,3-二甲基尿酸（p<0.03）、3-甲基黄嘌呤（p<0.04）和1-甲基尿酸（p<0.02）的游离代谢清除率显著降低。这些观察结果表明，正常老年人中茶碱的肾和代谢消除过程均不太活跃。
