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<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<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<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.
Get full access to this article
View all access options for this article.