Abstract
The mechanism of an interaction between theophylline and mexiletine hydrochloride was investigated in 6 male inpatients coadministered both drugs and 16 inpatients (13 men, 3 women) administered theophylline only. Serum theophylline and mexiletine concentrations and urinary concentrations of theophylline and its metabolites were monitored. Theophylline clearance was 0.0278 +/- 0.0047 L/kg/h (mean +/- SD) in patients coadministered theophylline and mexiletine and 0.0441 +/- 0.0096 in patients administered theophylline only (p less than 0.05). The fractional urine contents of 1-methyluric acid and 3-methylxanthine were 18.7 +/- 2.5 and 12.6 +/- 2.1 percent in the former group and 26.5 +/- 6.0 and 17.1 +/- 2.0 percent in the latter group, respectively (p less than 0.05). The fractional urine content of 1,3-dimethyluric acid was 51.8 +/- 3.2 in the former and 44.7 +/- 4.1 percent in the latter, respectively (p less than 0.05). An inverse correlation was obtained between serum mexiletine concentrations and total fractional urine content of 1-methyluric acid and 3-methylxanthine (r = 0.704). These results suggest that the mechanism of an interaction between theophylline and mexiletine is an inhibition of demethylation of theophylline by mexiletine.
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