The effect of tocainide on theophylline metabolism.
The effect of 5 days of oral tocainide (400 mg every 8 h) on the kinetics of theophylline given as a single 5 mg kg-1 i.v. infusion over 30 min was investigated in eight healthy male nonsmokers. Treatment with tocainide decreased the plasma clearance of theophylline from 37.5 +/- 6.9 (mean +/- s.d.) to 33.7 +/- 5.0 ml kg-1 h-1 (difference -3.8, 95% CI, -1.7 to -5.9; P = 0.004) and increased its terminal elimination half-life from 9.7 +/- 2.5 to 10.4 +/- 2.1 h (difference 0.7, 95% CI, 0.2 to 1.2; P = 0.011). Tocainide decreased the formation clearances of 3-methylxanthine and 1-methyluric acid, but the formation clearance of 1,3-dimethyluric acid was unaltered. These data indicate that tocainide exerts a modest inhibitory effect on theophylline metabolism. The magnitude of this change is substantially smaller than that reported to be produced by mexiletine.
Loi
C M
CM
Clinical Pharmacology and Gerontology Research Unit, Department of Veterans Affairs Medical Center, Boise, ID 83702.
Wei
X
X
Parker
B M
BM
Korrapati
M R
MR
Vestal
R E
RE
D000328:Adult; D004347:Drug Interactions; D006801:Humans; D008297:Male; D012907:Smoking / Q000097:blood; D013806:Theophylline / Q000097:blood*; D016677:Tocainide / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
D016677:Tocainide; D013806:Theophylline