Losartan, a selective angiotensin receptor antagonist, is mainly metabolized by CYP2C9 to an active carboxylic acid, E3174, which is pharmacologically more potent inhibitor than the parent compound. We evaluated the effect of bucolome, a CYP2C9 inhibitor, on the pharmacokinetics of losartan and E3174, which were measured by high performance liquid chromatography in human volunteers and rats. A randomized crossover design study with two phases was done in the volunteer study. In the first phase, the volunteers received losartan 25 mg alone orally (LOS group), and, in the second phase, losartan 25 mg was given after repeated oral administration of 300 mg bucolome for 7 days (LOS+BUC group). In the LOS group, the maximum concentration (C(max)) and area under the concentration curve (AUC) of losartan were significantly higher than in the LOS+BUC group. On the other hand, in the LOS+BUC group, the C(max) and AUC of E3174 were significantly lower than in the LOS group. In the rat study, male Wistar ST rats were used. In the first phase, the rats orally received losartan 10 mg/kg alone or after bucolome was given repeatedly at a dose of 20, 50, or 200 mg/kg for 7 days. In the second phase for steady state, the rats were given losartan 10 mg/kg for 14 days (group A) or losartan 10 mg/kg and bucolome 50 mg/kg for 14 days (Group B). Bucolome at doses 50 and 200 mg/kg significantly increased the AUC losartan and significantly decreased the AUC of 3174. At the steady state, there were no significant differences in AUC of losartan between Group A and B, but the C(max) and AUC of E3174 were significantly lower in Group B than Group A.