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 f or the treatment of asthma. The pharmacokinetics and dose proportional ity of ABT-761 after single doses (10-160 mg) of ABT-761 in 24 healthy male volunteers were investigated in a double-blind, placebo-controll ed study. The compound was well tolerated, with no clinically signific ant effects on vital sign measurements, hematological parameters, clin ical chemistry, urinalysis, or electrocardiogram. The plasma concentra tion-time profile of ABT-761 indicates that the drug declines in a mon oexponential fashion after moderately slow absorption, with a t(max) v alue of approximately 4 h. The terminal elimination t(1/2) averaged 15 h, and was dose independent. ABT-761 mean values of C-max and AUC wer e linearly related to drug dose. ABT-761 is well tolerated in healthy volunteers and the pharmacokinetics are linear in the single-dose rang e between 10 and 160 mg. (C) 1998 John Wiley & Sons, Ltd.