Azimilide pharmacokinetics and pharmacodynamics upon multiple oral dosing

Azimilide is a new, novel Class III antiarrhythmic drug that blocks slow and fast K⁺ channels. To assess dose proportionality, parallel groups of healthy subjects (ages 18 - 40 y) were administered drug for 14 days, with up to 3 days of loading. Doses were 35, 100, 150, or 200 mg qd. An older group (ages >55 y) received 100 mg qd. Blood was collected up to 72 h after the last dose. QTc was modeled as a marker of Class III activity. Mean results follow: Daily Cmax Cmin ClO Emax EC50 Dose ng/mL ng/mL L/kg/h %Δ ng/mL 35 mg 186 108 0.12 25 476 100 mg 514 337 0.13 27 460 150 mg 784 454 0.16 26 504 200 mg 1030 549 0.11 27 489 elderly 100 mg 536 335 0.11 24 542 Azimilide pharmacokinetics were dose proportional from 35 to 200 mg qd and did not differ among young and elderly subjects. Azimilide pharmacodynamics did not differ among study groups.

Duke Scholars

Author Hussein Rashid Al-Khalidi Biostatistics & Bioinformatics, Division of Biostatistics