*3.4. E*ff*ect of Metformin on Verapamil Pharmacokinetics*

The mean arterial plasma concentration–time profiles and relevant pharmacokinetic parameters of verapamil and norverapamil after intravenous administration of verapamil with and without metformin are shown in Figure 4 and Table 3, respectively. After intravenous and oral administration of verapamil with metformin, all pharmacokinetic parameters of verapamil and norverapamil including the AUCnorverapamil /AUCverapamil ratio were comparable to those without metformin. The absorption of verapamil from the gastrointestinal tract and the formation of norverapamil were rapid based on the *C*max of verapamil and norverapamil, respectively.

– ○ without (●) metformin to rats. The doses of metformin and verapamil were 30 and 20 mg/kg, **Figure 4.** Mean (± S.D.) arterial plasma concentration–time profiles of verapamil and norverapamil after intravenous (**A**, *n* = 6 for each) or oral (**B**, *n* = 5 for each) administration of verapamil with (#) or without (•) metformin to rats. The doses of metformin and verapamil were 30 and 20 mg/kg, respectively.


**Table 3.** Mean (± S.D.) pharmacokinetic parameters of verapamil and norverapamil after intravenous or oral administration of verapamil without and with metformin to rats. The doses of metformin and verapamil were 30 and 20 mg/kg, respectively.

AUC, total area under the plasma concentration−time curve from time zero to infinity; MRT, mean residence time; Vss, apparent volume of distribution at steady state; CL, time-averaged total body clearance; CLNR, time-averaged non-renal clearance; CLR, time-averaged renal clearance; Ae0–24 h, percentage of the dose excreted in the urine up to 24 h; GI24 h, percentage of the dose recovered from the gastrointestinal tract (including its contents and feces) at 24 h; *C*max, peak plasma concentration of docetaxel; *T*max, time to reach *C*max; *F*, extent of absolute oral bioavailability.
