Table 1.
Pharmacokinetic parameters in the systemic and portal circulations after i.v., i.p. and i.d. administration of different bile pigments
| Compound | K distributionα (nM·min−1) | t1/2α (min) | K eliminationβ (nM·min−1) | t1/2β (min) | Cmax (t0, µM) | Cpeak (µM) | AUC180 (µM·min) | Vd (L·kg−1) | Bioavailability (%)# | Biliary excretion (%)* | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| i.v. (2.7 mg·kg−1) | |||||||||||
| UCB (n = 7) | 76.8 ± 6.98 | 9.53 ± 0.95 | 6.46 ± 1.14 | 128 ± 21.3 | 54.7 ± 7.59 | 45.2 ± 5.78 | 969 ± 170 | 0.070 ± 0.002 | – | 29.1 ± 2.14 | |
| BV (n = 7) | 261 ± 18.3 | 2.79 ± 0.21 | 9.51 ± 2.37 | 103 ± 25.5 | 97.3 ± 6.57 | 59.5 ± 5.87 | 454 ± 53.8 | 0.069 ± 0.003 | – | 57.3 ± 1.70 | |
| BRT (n = 6) | 612 ± 39.5 | 1.16 ± 0.07 | 12.8 ± 4.11 | 74.7 ± 15.1 | 67.4 ± 9.46 | 19.3 ± 1.87 | 96.8 ± 12.3 | 0.055 ± 0.001 | – | 78.2 ± 4.98 | |
| i.p. (2.7 mg·kg−1) | |||||||||||
| UCB (n = 5) | – | – | – | – | – | 2.32 ± 0.20 | 250 ± 20.0 | – | 14.0 | 38.2 ± 4.74 | |
| BV (n = 4) | – | – | – | – | – | 0.63 ± 0.14 | 73.0 ± 12.0 | – | 16.1 | 27.6 ± 3.17 | |
| BRT (n = 6) | – | – | – | – | – | 0.23 ± 0.07 | 32.0 ± 7.29 | – | 33.1 | 34.1 ± 8.06 | |
| i.d. (27 mg·kg−1) | |||||||||||
| UCB | Systemic (n = 15) | – | – | – | – | – | 1.52 ± 0.14 | 188 ± 14.7 | – | 1.0 | 2.72 ± 0.43 |
| Portal (n = 6) | – | – | – | – | – | 2.39 ± 0.32 | 306 ± 40.2 | – | 2.0 | ||
| BV | Systemic (n = 9) | – | – | – | – | – | 0.29 ± 0.09 | 29.7 ± 8.13 | – | 0.7 | 0.21 ± 0.31 |
| Portal (n = 3) | – | – | – | – | – | 0.33 ± 0.28 | 19.4 ± 14.0 | – | 0.4 | ||
| BRT | Systemic (n = 10) | – | – | – | – | – | 0.29 ± 0.26 | 21.8 ± 11.0 | – | 2.3 | 4.61 ± 1.13 |
| Portal (n = 4) | – | – | – | – | – | 1.12 ± 1.02 | 55.0 ± 42.6 | – | 5.7 | ||
Data shown are mean ± SEM.
*
Biliary bile pigment excretion in the treatment groups have been corrected by subtracting the endogenous bile pigment excretion in the respective vehicle group.
#
The bioavailability of unconjugated bilirubin has been corrected for the endogenous unconjugated bilirubin AUC180 in the vehicle groups.
UCB, unconjugated bilirubin; BV, biliverdin; BRT, bilirubin ditaurate.