TABLE 3

Comparison of pharmacokinetic parameters in KHB- and rbc-alb-perfused livers and fits of data to compartmental models (Fig. 3) to arrive at the microconstants: k12, k21, ke, km, k10, and k20 The optimal weighting scheme of unity was used.




KHB-Perfused Livers

Rbc-Alb-Perfused Livers (20% rbc-1% Albumin)
Rat weight (g) 292 ± 3 327 ± 28a
Liver weight (g) 11.2 ± 1.4 12.3 ± 2.0
Hematocrit 0 0.14 ± 0.02a
Flow rate (ml/min) 40 ± 0 10 ± 0
Recovery of perfusate volume (% initial volume) 89 ± 5 91 ± 2
Recovery of radioactivity (% dose at 3 h)
   Total bile 39 ± 17 25 ± 13
      Bile: Dg3 11 ± 8 5 ± 2
      Bile: Dg2 19 ± 10 14 ± 8
   Total perfusate 16 ± 5 28 ± 18
      Perfusate: Dg3 11 ± 1 23 ± 13
      Perfusate: Dg2 3 ± 2 5 ± 5
   Liver tissue 38 ± 27 18 ± 1
   Total recovery 93 ± 19 71 ± 13
Noncompartmental analysis
   AUC (from trapezoidal method) 7985 ± 2374 12362 ± 6938
   CLliver,tot 0.192 ± 0.049 0.123 ± 0.061
   CLliver,tot/fb 0.192 ± 0.049 0.200 ± 0.098
Fits to elimination from central compartment
   k12 (min–1) 0.379 ± 0.273b 0.141 ± 0.128
   k21 (min–1) 0.137 ± 0.152 0.242 ± 0.224
   k10 (min–1) 0.017 ± 0.006 0.0089 ± 0.0035
   ke (min–1) 0.0039 ± 0.0026 0.0007 ± 0.003a
   km (min–1) 0.013 ± 0.004 0.0082 ± 0.0032
   MSC 16.5 ± 0.52 13.3 ± 0.71a
   CLliver,met (ml/min/g) 0.185 ± 0.049 0.105 ± 0.052
   CLliver,ex (ml/min/g) 0.059 ± 0.045 0.009 ± 0.005
   CLliver,tot (ml/min/g) 0.244 ± 0.082 0.114 ± 0.057a
   CLliver,tot/fb (ml/min/g) 0.244 ± 0.082 0.185 ± 0.093
   E 0.066 ± 0.017 0.133 ± 0.052
   CLint,sec (ml/min/g) 0.060 ± 0.047 0.015 ± 0.009
   CLint,met (ml/min/g) 0.196 ± 0.054 0.198 ± 0.103
Fits to elimination from peripheral compartment
   k12 (min–1) 0.349 ± 0.288 0.171 ± 0.115
   k21 (min–1) 0.190 ± 0.169 0.321 ± 0.196
   k20 (min–1) 0.008 ± 0.006 0.018 ± 0.004a
   ke (min–1) 0.0017 ± 0.0015 0.0014 ± 0.0004
   km (min–1) 0.0062 ± 0.0060 0.016 ± 0.004a
   MSC 13.6 ± 2.85 13.2 ± 0.86
   CLliver,met (ml/min/g) 0.140 ± 0.069 0.108 ± 0.045
   CLliver,ex (ml/min/g) 0.058 ± 0.050 0.010 ± 0.005
   CLliver,tot (ml/min/g) 0.198 ± 0.111 0.117 ± 0.051
   CLliver,tot/fb (ml/min/g) 0.198 ± 0.111 0.191 ± 0.083
   E 0.053 ± 0.023 0.138 ± 0.043a
   CLint,sec (ml/min/g) 0.059 ± 0.052 0.016 ± 0.009
   CLint,met (ml/min/g)
0.146 ± 0.052
0.203 ± 0.091
  • a P < 0.05 parameters in rbc-alb-perfused livers compared with those in KHB-perfused livers

  • b Mean ± S.D.; n = 4