Theophylline pharmacokinetics in normal elderly subjects.
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.
Shin
S G
SG
Clinical Research Center, Northwestern Memorial Hospital, Chicago, Ill.
Juan
D
D
Rammohan
M
M
D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013806:Theophylline / Q000493:pharmacokinetics*; D014527:Uric Acid / Q000031:analogs & derivatives / Q000652:urine; D014970:Xanthines / Q000652:urine
D014970:Xanthines; D014527:Uric Acid; C030530:1-methyluric acid; D013806:Theophylline; C031274:1,3-dimethyluric acid; C029703:3-methylxanthine