Co-Administration of Diltiazem Significantly Increases the Plasma Exposure of Tamsulosin

Tamsulosin, a selective α1-adrenoceptor antagonist, is extensively metabolized by CYP3A4 and CYP2D6 isozyme. Diltiazem is known as a moderate inhibitor of CYP3A4. In this study, the effects of co-administration of diltiazem on the pharmacokinetics of tamsulosin were investigated. Ten healthy subjects genotypes as CYP2D6*wt/*wt (*wt= *1 or *2) were recruited for the study. In the control phase, each subject received a 0.2 mg oral dose of tamsulosin. In the diltiazem phase, they received 60 mg diltiazem three-times daily fot four days. In the study (day 3), all volunteers received a 0.2 mg oral dose of tamsulisin, one hour after the morning dose of diltiazem was ingested. Blood samples were collected up to 48 hr after drug intake in each phase, and plasma concentrations of tamsulosin were determined by validated HPLC-MS/MS method. In the diltiazem phase, C_max and AUC_inf of tamsulosin were both 1.71-fold increased than those in the control phase (both P<0.0001). AUC_inf of tamsulosin in the control phase and in the diltiazem phase was 48.2±14.1 ng hr/mL, respectively. Oral clearance (CL/F) of tamsulosin in the diltiazem phase (2.6±0.6 L/hr) was also significantly decreased than that in the control phase (4.4±1.1 L/hr, P<0.0001). Co-administration of diltiazem significantly inhibits  the metabolism of tamsulosin mediated by CYP3A4, leading to an increase in the plasma exposure of tamsulosin.