TABLE 2

Experimentally derived parameters with different verapamil initial concentrations delivered to the recirculating, RBC-perfused rat liver preparation at 12 ml/min

ParametersIntended and Measured Verapamil Concentrations at t = 0 (μM) (n = 4)P value
1 μM (0.947 ± 0.064)50 μM (47.5 ± 1.8)100 μM (103 ± 0.7)
Embedded Image (ml/min)10.5 ± 1.38.34 ± 0.608.91 ± 2.270.244
Embedded Image (ml/min)0.288 ± 0.0430.180 ± 0.020.163 ± 0.0430.012 a
Embedded Image (ml/min)10.2 ± 1.38.16 ± 0.638.75 ± 2.270.274
Embedded Image (ml/min)0.118 ± 0.0290.012 ± 0.0040.022 ± 0.009<0.0001 a
Embedded Image (ml/min)10.1 ± 1.38.15 ± 0.638.73 ± 2.270.285
Embedded Image 0.850 ± 0.1070.680 ± 0.0530.729 ± 0.1890.282
Embedded Image 0.150 ± 0.1070.320 ± 0.0530.271 ± 0.1890.365
Embedded Image b 0.027 ± 0.008NA d NANA
Embedded Image 0.012 ± 0.003NANANA
Embedded Image c 0.232 ± 0.189NANANA
  • a Significant difference between 1, 50, and 100 μM verapamil dosing groups; P < 0.05.

  • b Fraction of hepatic clearance of verapamil that furnishes norverapamil to circulation (Pang and Kwan, 1983); preformed norverapamil data are from Table 3.

  • c Fraction of hepatic clearance of verapamil that forms norverapamil, where Embedded Image is the hepatic availability of preformed norverapamil at the lowest dose from Table 3.

  • d Not available.