Single-Dose, Steady-State Pharmacokinetics of Seratrodast (AA-2414) in Healthy Male and Female Volunteers
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The primary objectives of this randomised, placebo-controlled, double-blind, parallel-group study were to evaluate the tolerability and pharmacokinetic characteristics of repetitive, oral, total daily doses of 160, 240 or 320mg of seratrodast administered in a once-daily regimen to healthy male and female volunteers. A total of 24 volunteers (12 males and 12 females) received seratrodast and another 11 study participants received placebo. Study drug was administered once daily on study day 1 and study days 3 through 9 after overnight fasting. Blood samples were collected on days 1 and 9. The plasma concentrations of seratrodast increased proportionally with dose between the 160 and 240mg doses with some evidence (mainly after single doses) of a less than proportional increase at the 320mg dose level. The reason for the lack of dose proportionality could be due to saturation of the protein binding sites and/or decreased absorption at higher doses. The oral clearance and terminal half-life averaged 0.9 L/h (28% CV) and 20 hours (46% CV), respectively, after single-dose administration. As expected from the terminal half-life, seratrodast accumulated predictably upon once-daily multiple administration, and steady-state was ultimately reached within 7 days of administration. A gender effect was observed for peak plasma concentrations (Cmax), and area under the plasma concentration versus time curve (AUC) on day 9, with females having higher concentrations than males. Seratrodast was found to be well tolerated after repeated multiple doses of up to 320 mg/day.
KeywordsAdis International Limited Drug Invest Plasma Drug Concentration Total Daily Dose Female Volunteer
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- 3.Hiraga K, Tateno M. The clinical phase I study of AA-2414, a thromboxane A2 receptor antagonist — repeated-dose study at 160mg once daily for 7 days. Clin Pharmacol 1993; 9 Suppl. 8: 41–55Google Scholar
- 4.Samara E, Granneman R, Locke C, et al. Pharmacokinetics and pharmacodynamics of seratrodast in patients with moderate asthma. Clin Pharmacol Ther 1997. In PressGoogle Scholar
- 5.Gibaldi M, Perrier D. Pharmacokinetics. 2nd ed. New York: Marcel Dekker, 1982Google Scholar