The effect of histamine-2 receptor antagonists on tocainide pharmacokinetics.
The effects of cimetidine and ranitidine on tocainide pharmacokinetics were assessed in seven healthy subjects, using a randomized, double-blind, placebo-controlled, cross-over study design. After a 400-mg oral dose of tocainide, the area under the concentration-time curve decreased from (mean +/- SD) 31.64 +/- 14.16 micrograms.hr/mL during placebo, to 23.10 +/- 7.33 micrograms.hr/mL during cimetidine (P less than .05). Similarly, the peak tocainide concentrations were 2.81 +/- 0.89 micrograms/mL and 1.70 +/- 0.44 micrograms/mL with placebo and cimetidine, respectively (P less than .05). There was no change in the above parameters between ranitidine and placebo. The terminal half-life and renal clearance of tocainide were not altered by either H2-receptor antagonists, compared with placebo. However, the total amount of tocainide excreted unchanged in the urine, decreased from 159.8 +/- 14.7 mg with placebo to 136.8 +/- 26.8 mg with cimetidine (P less than .05), whereas there was no change with ranitidine. These data indicate that cimetidine, but not ranitidine, causes a decrease in the bioavailability of tocainide and that neither agent alters the apparent elimination rate of tocainide.
North
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Department of Medicine, Wyoming Medical Center, Casper.
Mattern
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Kapil
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Lalonde
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D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics*; D002927:Cimetidine / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006207:Half-Life; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D008012:Lidocaine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D011899:Ranitidine / Q000494:pharmacology; D016677:Tocainide
D000889:Anti-Arrhythmia Agents; D006635:Histamine H2 Antagonists; D016677:Tocainide; D002927:Cimetidine; D011899:Ranitidine; D008012:Lidocaine