Abstract
To the Editor. —Monahan et al 1 reported a case of torsades de pointes after concomitant administration of terfenadine (Seldane) and ketoconazole (Nizoral). We would like to comment on this report and share results from subsequent studies at Marion Merrell Dow Inc, Kansas City, Mo. Terfenadine normally undergoes extensive (99%) first-pass metabolism to two metabolites: an active acid metabolite and an inactive dealkylated metabolite. Therefore, unchanged terfenadine is normally undetectable (ie, 2 In a study of 24 subjects given a single 60-mg dose of terfenadine, the mean peak plasma acid metabolite level was 263 ng/mL and occurred 2.5 hours after dosing.
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