Effects of diltiazem on plasma and tissue digoxin levels in mice

Effects of diltiazem hydrochloride (DTZ) on digoxin (DX) concentrations in plasma and tissues (brain, heart, liver, and kidney) were studied in mice, and the effects were compared with those of quinidine sulfate (QD). When DX (0.2 mg/kg) was coadministered with DTZ (60 mg/kg) orally for 5 d to mice, plasma DX concentrations were increased significantly as with QD (100 mg/kg). Tissue DX concentrations were also increased in brain, heart, and liver. However, the DX tissue/plasma concentration (T/P) ratios for brain, heart, and kidney were rather decreased with DTZ or QD. The increased plasma and tissue DX concentrations and the decreased T/P ratios with DTZ might be responsible for both the displacement of tissue DX binding and reduced DX elimination as with QD.