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Kinetics and dynamics of sematilide
1Department of Clinical Pharmacology, Berlex Laboratories, Wayne, New Jersey 07470, USA.
Therapeutic Drug Monitoring
|October 1, 1995
Summary
Sematilide HCl, a novel antiarrhythmic drug, showed good tolerability in volunteers. Pharmacokinetic and QTc interval effects were evaluated after intravenous and oral administration, revealing its excretion and bioavailability.
Area of Science:
- Pharmacology
- Clinical Pharmacology
- Cardiology
Background:
- Sematilide HCl is a novel Class III antiarrhythmic agent.
- Understanding its pharmacokinetic and pharmacodynamic properties is crucial for clinical application.
Purpose of the Study:
- To determine the pharmacokinetics, QTc interval effect, and tolerability of sematilide HCl.
- To assess the drug's behavior after both intravenous and oral administration.
Main Methods:
- Utilized high-performance liquid chromatography for plasma and urine concentration measurements.
- Employed a compartment model-independent approach for pharmacokinetic analysis.
- Investigated the concentration-QTc relationship, including hysteresis, using a semiparametric model.
Main Results:
- Sematilide HCl demonstrated a bioavailability of 0.47.
- Unchanged drug excretion in urine was 75.1% after IV and 36.0% after oral administration.
- A maximum QTc interval effect of 12% was observed with a 14-minute delay post-IV infusion.
Conclusions:
- Sematilide HCl was well tolerated in healthy volunteers.
- Pharmacokinetic-pharmacodynamic modeling, accounting for hysteresis, provided a suitable fit.
- The study provides essential data for further development of sematilide HCl.