Abstract:
: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 steady-state (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-year-old and > 55-year-old subjects. Pharmacodynamics did not differ across dose groups. The mean maximum effect (Emax) ranged from 24 to 28% change in QTc from baseline. The concentration needed to attain one half Emax 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.
journal_name
Biopharm Drug Disposjournal_title
Biopharmaceutics & drug dispositionauthors
Corey A,Al-Khalidi H,Brezovic C,Marcello S,Parekh N,Taylor K,Karam Rdoi
10.1002/(sici)1099-081x(199903)20:2<59::aid-bdd155keywords:
subject
Has Abstractpub_date
1999-03-01 00:00:00pages
59-68issue
2eissn
0142-2782issn
1099-081Xpii
10.1002/(SICI)1099-081X(199903)20:2<59::AID-BDD155journal_volume
20pub_type
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