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[Effect of serum albumin concentration on percentage of free theophylline fraction].

The authors experienced three cases in which serum free theophylline concentrations (F) rose with unchanged or decreased serum total theophylline concentrations (T). To clarify the causes of changes in F or T within a short time, we studied the relationship between F and serum albumin concentration or T in patients, and the relationship between T and F using aminophylline alone or aminophylline and cefazoline (CEZ) in rabbits. In patients, the fraction of free theophylline (F/T) showed a reverse relation to the serum albumin concentration, and a positive relation to T. In rabbits, when aminophylline was injected with CEZ, F/T increased in proportion to the dose of CEZ and T decreased when aminophylline alone was injected. The data suggested that F/T increased accompanied with decreasing serum albumin concentration or increasing T, since the albumin binding-site of theophylline is limited. The present study also suggested that the protein-bound theophylline decreased in competition with CEZ, therefore F/T increased when aminophylline was injected with CEZ. It is likely that decreased T is a result of augmented movement of theophylline to the tissue due to decreased serum albumin concentration. To evaluate the clinical conditions of the patients taking theophylline, it is necessary to directly monitor F, or to measure serum albumin concentration if direct measurement of F is not possible.