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 |