Dose-proportional pharmacokinetics of a new 5-lipoxygenase inhibitor, ABT-761, in healthy volunteers.
ABT-761, a new potent 5-lipoxygenase inhibitor, is under development for the treatment of asthma. The pharmacokinetics and dose proportionality of ABT-761 after single doses (10-160 mg) of ABT-761 in 24 healthy male volunteers were investigated in a double-blind, placebo-controlled study. The compound was well tolerated, with no clinically significant effects on vital sign measurements, hematological parameters, clinical chemistry, urinalysis, or electrocardiogram. The plasma concentration-time profile of ABT-761 indicates that the drug declines in a monoexponential fashion after moderately slow absorption, with a tmax value of approximately 4 h. The terminal elimination t1/2 averaged 15 h, and was dose independent. ABT-761 mean values of Cmax and AUC were linearly related to drug dose. ABT-761 is well tolerated in healthy volunteers and the pharmacokinetics are linear in the single-dose range between 10 and 160 mg.
Wong
S L
SL
Abbott Laboratories, Abbott Park, IL 60064-3500, USA. shekman.wong@abbott.com
Drajesk
J
J
Chang
M S
MS
Witt
G
G
Awni
W M
WM
D000328:Adult; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D006918:Hydroxyurea / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016859:Lipoxygenase Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D010919:Placebos
D016859:Lipoxygenase Inhibitors; D010919:Placebos; C096921:atreleuton; D006918:Hydroxyurea