Enterohepatic recirculation of the new antihypertensive drug UP 269-6 in humans. A possible model to account for multiple plasma peaks.

Abstract

Following a single dose of a new antihypertensive drug, UP 269-6 (5-methyl-7-propyl-8-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl)methyl]-1,2,4-triazolo[1,5-c]pyrimidin-2(3H)-one, CAS 148504-51-2), to 12 healthy volunteers, the plasma levels showed at least two secondary peaks. To explain this observation, the data were fitted to a new compartmental model of enterohepatic recirculation, without using a numerical method. Most subjects exhibited two cycles of recirculation. The amount of drug involved in each recirculation was calculated and the AUCs compared. The drug showed high biliary excretion and reabsorption.