Mechanism of interaction between theophylline and mexiletine.
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.
Ueno
K
K
Department of Pharmacy, National Sengokuso Hospital, Osaka, Japan.
Miyai
K
K
Kato
M
M
Kawaguchi
Y
Y
Suzuki
T
T
D000368:Aged; D000369:Aged, 80 and over; D001499:Bayes Theorem; D004347:Drug Interactions; D016231:Fluorescence Polarization Immunoassay; D006801:Humans; D008297:Male; D008801:Mexiletine / Q000009:adverse effects*; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D014527:Uric Acid / Q000031:analogs & derivatives / Q000652:urine; D014970:Xanthines / Q000652:urine
D014970:Xanthines; D008801:Mexiletine; D014527:Uric Acid; C030530:1-methyluric acid; D013806:Theophylline; C029703:3-methylxanthine