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On a multiple‐dose schedule of oral aminophylline (200 to 300 mg. every 6 hours) “trough” levels of serum theophylline in 83 patients ranged from 2.9 to 32.6 µg per milliliter. Levels usually remained in the same range for each individual. Kinetic studies demonstrate dependence of the mean serum level during multiple dosing on the intravenous theophylline half‐life. Theophylline renal clearances are small and constant. Thus, wide variations in metabolism appear to be chiefly responsible. Specific studies are needed to document this and to assess the contribution of absorption variables. Persistent nausea, vomiting, or anorexia were common with trough levels over 20 flg per milliliter but were not seen when trough levels were under 13 µg per milliliter. This suggests that these gastrointestinal side effects usually arise by some mechanism mediated through serum theophylline levels rather than from direct irritation of the gastric mucosa. Serial airway resistances in 7 asthmatic patients following a large single oral dose of aminophylline indicated that the minimum theophylline level required for maximum bronchodilator effect ranged between eight and 20 µg per milliliter. To achieve trough concentrations of 10 to 20 µg per milliliter, final dosage adjustments ranged from 400 to 3,200 mg. of aminophylline per 24 hours, averaging 1,200 mg. General guidelines are offered for aminophylline dose adjustment.
Jenne et al. (Mon,) studied this question.