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Theophylline pharmacokinetics in normal elderly subjects
Author(s) -
Shin SangGoo,
Juan David,
Rammohan Meenakshi
Publication year - 1988
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1988.189
Subject(s) - theophylline , pharmacokinetics , volume of distribution , renal function , clearance , free fraction , creatinine , medicine , endocrinology , bronchodilator , chemistry , volunteer , renal physiology , excretion , plasma clearance , asthma , urology , agronomy , biology
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 t ½ . The unbound fraction of theophylline was significantly raised in the elderly (mean 77.7% vs. 62.3%, p < 0.001) and was correlated with the serum albumin level ( r = −0.7, p < 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 < 0.05). Creatinine clearance was reduced in the elderly and was significantly correlated with unbound renal clearance ( r = 0.6, p < 0.04). There were no age‐related differences in the urinary excretion of theophyUine, 1‐methyluric acid, 3‐methylxanthine, or 1,3‐dimethyluric acid. However, significant reduction in unbound renal theophyUine clearance ( p < 0.002) as well as the unbound metabolic clearance of 1,3‐dimethyluric acid ( p < 0.03), 3‐methylxanthine ( p < 0.04), and 1‐methyluric acid ( p < 0.02) were observed in the elderly subjects. These observations indicate that both renal and metabolic elimination processes for theophyUine are less active in the normal elderly. Clinical Pharmacology and Therapeutics (1988) 44, 522–530; doi: 10.1038/clpt.1988.189