Biovailability and pharmacokinetics of femoxetine

The availability of trans-(+)-3-[(4-methoxy-phenoxy)methyl]-1-methyl-4-phenylpiperidine (femoxetine, HCl; 500 mg) from an enteric coated tablet and from a water solution, respectively, have been compared in a single dose, cross-over study using six healthy volunteers. The tablet gave a longer lag time and a slower absorption rate than the solution. The mean availability of the tablet was 71% (range 12-150%), relative to the availability of the solution in five of the subjects. During a multiple dose study, where the same six volunteers took 400-600 mg (as tablets) per day for a week, no change in the kinetic parameters was observed and no discrepancy between the parameters obtained in the single dose study and the ones from the multiple dose study was seen within each subject. A high first pass effect is presumed to be the main reason for the relatively great inter-individual variations. The formation and elimination rate of an active metabolite, norfemoxetine, were very similar in three of the four subjects for whom the rates could be calculated.