Tolerance and Effects of Almokalant, a New Selective Ik Blocking Agent, on Ventricular Repolarization and on Sino-Atrial and Atrioventricular Nodal Function in the Heart

Darpö, Börje; Almgren, Olle; Bergstrand, Robert; Bäärnhielm, C; Gottfridsson, Christer; Sandstedt, Bengt; Edvardsson, Nils

doi:10.1097/00005344-199505000-00001

Cited by 14 publications

(9 citation statements)

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“…The only noted side effect, besides the proarrhythmic events, has been a transient metallic taste, most often observed at high plasma levels. This was reported by 1 healthy subject after infusion of 9.6 pmol and by 3 of 4 subjects after a 25.6 prnol infusion (24). The same phenomenon was reported by 2 subjects who received bolus infusions aiming at plasma concentrations ( C , ) of 50 and 100 nmoYL.…”

Section: Tolerabilitysupporting

confidence: 76%

“…Increasing doses of almokalant (0.1-25.6 Fmol, 2 4 individuals at each dose level) were given i.v. over 10 minutes to healthy volunteers (24). The C,,, values obtained directly after the end of the infusion showed a large individual variation and correlated poorly with the increase in dose, which indicated a rapid distribution to extravascular tissues.…”

Section: Human Studiesmentioning

confidence: 91%

“…Prolongation of the AERP has been demonstrated in healthy volunteers using both transesophageal atrial stimulation (TAS) (24) and an invasive technique (26). Using TAS, the AERP increased from 294 ms to 316 ms at 100 bpm (+7%, p = 0.009) and from 284 to 321 ms at 120 bpm ( + 13%, p = 0.003) at a mean plasma concentration of approximately 100 nmol/L.…”

Section: The Effective Refractory Period Of the Atria (Aerp)mentioning

confidence: 99%

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Almokalant—A Selective Class III Antiarrhythmic Compound

Darpö

Almgren²

1996

Cardiovascular Drug Reviews

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Section: Tolerabilitysupporting

confidence: 76%

Section: Human Studiesmentioning

confidence: 91%

Section: The Effective Refractory Period Of the Atria (Aerp)mentioning

confidence: 99%

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Almokalant—A Selective Class III Antiarrhythmic Compound

Darpö

Almgren²

1996

Cardiovascular Drug Reviews

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“…Almokalant in high doses causes changes in T-wave morphology in certain individuals [7,8]. It cannot be ruled out that the difference in QT prolongation during stimulation in the RVAPEX and RVOT would in part be explained by different degree of T-wave flattening in the selected leads.…”

Section: Limitationsmentioning

confidence: 99%

“…To what extent this reverse frequency dependence will limit the clinical usefulness of putative antiarrhythmic agents will be the subject of future studies. The effects of almokalant on cardiac electrophysiology in humans have been studied with transesophageal atrial stimulation [7], as well as invasively with recordings of monophasic action potentials [8]. In healthy individuals, almokalant increased the ventricular paced MAPD by 20% at a plasma concentration of approximately 120 nmol/1.…”

mentioning

confidence: 99%

Assessment of frequency dependency of the class III effects of almokalant: A study using programmed stimulation and recording of monophasic action potentials and ventricular paced QT intervals

Darpö

Almgren²,

Bergstrand³

et al. 1996

Cardiovasc Drug Ther

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The aim of the present study was to assess the frequency dependency of the effects of almokalant, a selective class III antiarrhythmic drug, on ventricular repolarization using recordings of monophasic action potentials and measurements of ventricular paced QT intervals. Twenty male volunteers were studied during almokalant infusion aiming at plasma concentrations (Cpl) of 20, 50, 100, and 150 nmol/l. The duration of monophasic action potential at 90% repolarization (MAPD) was measured during incremental and premature ventricular extrastimulation. The ventricular paced QT interval was measured during incremental stimulation from the apical region (RV APEX) and the outflow tract (RVOT) of the right ventricle, and the frequency dependence was analyzed using a linear regression model. At an almokalant dose of Cpl > or = 50, there was a significant prolongation of the MAPD of 10-15%. The prolongation was of equal magnitude at all paced cycle lengths (CL). The MAPD of ventricular extrasystole increased in parallel over the range of coupling intervals studied and was significantly prolonged at Cpl 100 and 150. The ratio between the MAPD of the extrasystoles and preceding beats was unaltered after almokalant infusion. The ventricular paced QT intervals increased during almokalant infusion in a similar manner as that of the MAPD. During RV APEX stimulation, the prolongation was more pronounced at low heart rates, an effect that was not seen during RV OT stimulation. Almokalant significantly prolonged the MAPD at dose levels Cpl > or = 50. There was no evidence of a frequency dependence of this effect. The ventricular paced QT intervals were prolonged in a similar manner as that of the MAPD, and this effect exhibited a small reverse frequency dependence during RV APEX stimulation.

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