Azimilide pharmacokinetics and pharmacodynamics upon multiple oral dosing

✍ Scribed by Alfred Corey; Hussein Al-Khalidi; Christopher Brezovic; Stephen Marcello; Nikhil Parekh; Kevin Taylor; Roger Karam

• Book ID: 101279437
• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 194 KB
• Volume: 20
• Category: Article
• ISSN: 0142-2782
• DOI: 10.1002/(sici)1099-081x(199903)20:2<59::aid-bdd155>3.0.co;2-6

✦ Synopsis

This study assessed steady-state azimilide pharmacokinetics and pharmacodynamics in 119 healthy male and female volunteers. Parallel groups of 18 -40-year-old subjects received doses of 35, 100, 150 or 200 mg day -1 for up to 14 days, with 1, 2 or 3 days of loading. Another group of \55-year-old subjects received 100 mg day -1 with a 3-day loading regimen. There was a slight overshoot of steadystate (24%) after loading, but concentrations decreased to steady-state by day 7. Mean peak steady-state azimilide concentrations ranged from 186 to 1030 ng mL -1 across the 35 -200 mg day -1 dose range, while mean trough steady-state azimilide concentrations ranged from 108 to 549 ng mL -1 . Azimilide pharmacokinetics were proportional to dose, except for renal clearance, and did not differ between 18 -40-yearold and \55-year-old subjects. Pharmacodynamics did not differ across dose groups. The mean maximum effect (E max ) ranged from 24 to 28% change in QT c from baseline. The concentration needed to attain one half E max ranged from 432 to 542 ng mL -1 across dose groups. Equilibration was rapid between blood and the biophase, with equilibration half-lives of less than 1 min.