TY - JOUR
T1 - Pharmacology of the class 111 antiarrhythmic agent sematilide in patients with arrhythmias
AU - Wong, Wilson
AU - Paviou, Harris N.
AU - Birgersdotter, Ulrika M.
AU - Hillernan, Daniel E.
AU - Mohiuddin, Syed M.
AU - Roden, Dan M.
N1 - Funding Information:
From the Departments of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee,a nd the Cardiac Center, Creighton University, Omaha, Nebraska. This study was sup ported in part by grants from the United States Public Health Service, Bethesda, Maryland (HL32694 and General Clinical Research Center Award RR095 from the Division of Research Resources), and by Berlex Pharmaceuticals, Cedar Knolls, New Jersey. Manuscript received April 26, 1991; revised manuscript received and accepted September 20,199l.
PY - 1992/1/15
Y1 - 1992/1/15
N2 - Sematilide, a close structural analog of N-acetylprocainamide, prolongs cardiac action potentials in vitro, whereas it does not depress maximum action potential upstroke slope, a "class III" action. This report outlines an evaluation of the clinical pharmacologic actions of sematilide in 14 patients with chronic high-frequency nonsustained ventricular arrhythmias. In all, 36 intravenous infusions (range 0.15 to 1.5 mg/kg over 15 minutes) were administered in a dose-ranging, placebo-controlled study design. Sematilide prolonged rate-corrected QT (QTc) in a dose- and concentration-related fashion, did not alter PR or QRS, and slowed heart rate at high concentrations (≥2 μg/ml). The relations between dose and total area under the time-concentration curve, dose and peak plasma concentration, and peak plasma concentration and increase in QTc were linear (r = 0.66 to 0.92; p
AB - Sematilide, a close structural analog of N-acetylprocainamide, prolongs cardiac action potentials in vitro, whereas it does not depress maximum action potential upstroke slope, a "class III" action. This report outlines an evaluation of the clinical pharmacologic actions of sematilide in 14 patients with chronic high-frequency nonsustained ventricular arrhythmias. In all, 36 intravenous infusions (range 0.15 to 1.5 mg/kg over 15 minutes) were administered in a dose-ranging, placebo-controlled study design. Sematilide prolonged rate-corrected QT (QTc) in a dose- and concentration-related fashion, did not alter PR or QRS, and slowed heart rate at high concentrations (≥2 μg/ml). The relations between dose and total area under the time-concentration curve, dose and peak plasma concentration, and peak plasma concentration and increase in QTc were linear (r = 0.66 to 0.92; p
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U2 - 10.1016/0002-9149(92)91306-O
DO - 10.1016/0002-9149(92)91306-O
M3 - Article
C2 - 1731461
AN - SCOPUS:0026593345
SN - 0002-9149
VL - 69
SP - 206
EP - 212
JO - American Journal of Cardiology
JF - American Journal of Cardiology
IS - 3
ER -