Parameter | No albumin | BSA | HSA | HSAFAF | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0.1% | 1.0% | 2.0% | 0.1% | 1.0% | 2.0% | 0.1% | 1.0% | 2.0% | ||||||||
UGT1A1 | ||||||||||||||||
Km (μM) or Ks | 59 | 249a | 350a | 393a | 92 | 153 | 174 | 51 | 50 | 48 | ||||||
Vmax (pmol/min · mg) | 374 | 722a | 687a | 960a | 406 | 363 | 380 | 407 | 398 | 390 | ||||||
CLint (μl/min/mg) | 6.3 | N.A. | N.A. | N.A. | 4.4 | 2.4 | 2.2 | 8.0 | 8.0 | 8.1 | ||||||
UGT1A6 | ||||||||||||||||
Ksa | 78 | 71 | 95 | 93 | 81 | 102 | 176 | 91 | 64 | 65 | ||||||
Vmax (pmol/min · mg)a | 82,151 | 81,036 | 80,826 | 80,766 | 86,483 | 87,060 | 76,432 | 72,850 | 70,023 | 73,002 | ||||||
αa | 0.46 | 0.44 | 0.47 | 0.33 | 0.36 | 0.38 | 0.078 | 0.46 | 0.52 | 0.26 | ||||||
UGT1A9 | ||||||||||||||||
Km (μM) | 13.4 | 10.8 | 7.6 | 3.8 | 16.6 | 20.5 | 22.8 | 9.8 | 4.2 | 2.9 | ||||||
Vmax (pmol/min · mg) | 8362 | 7860 | 11262 | 9817 | 8422 | 8632 | 8649 | 8067 | 10265 | 9765 | ||||||
CLint (μl/min/mg) | 624 | 728 | 1482 | 2583 | 507 | 421 | 379 | 823 | 2444 | 3367 |
N.A., not applicable.
↵ a Data from fitting to a two-site model (Uchaipichat et al., 2004). The two-site model provides an estimate of binding affinity (Ks) rather than Km. α and β values for 4MU glucuronidation by recombinant UGT1A1 in the presence of 0.1, 1, and 2% BSA were 0.20 and 0.37, 0.034 and 0.45, and 0.063 and 0.27, respectively. The value of β was set at 2 for the modeling of 4MU glucuronidation by UGT1A6 because for autoactivation Vmax is equivalent to 2Kp[E]t (Uchaipichat et al., 2004).