It does not really seem to make a major difference to me, but I do think standing up helps the medicine spread out possibly more and drop to the lower anal area. That is just my opinion. I have been taking these on and off with canasa forever and my cuffitis is still pretty active. I wish I had a better answer for those of us suffering with this chronic, debilitating condition. I have recently started oral pentasa to see if this gives me the little extra boost I need to try and get my cuffitis in remission.