TABLE 4

Fold difference and fmUGT estimates obtained for 10 drugs obtained in the presence of BSA using individual P450 and UGT cofactors


Compound

-Fold Difference: Clint, u + BSA/CLint, u - BSA

In Vitro fmUGT + BSAa

In Vivo fmUGTb
P450
UGT
Buprenorphine 0.7 0.9 0.44 0.50
Carvedilol 1.1 7.9 0.50 N.A.
Codeine 0.8 3.2 0.81 0.82
Diclofenac 4.1 4.7 0.65 N.A.
Gemfibrozil 7.4 12.1 0.86 0.40
Ketoprofen 1.8 4.5 0.71 0.90
Midazolam 3.7 N.D. N.D. N.A.
Naloxone 0.6 2.6 0.89 0.65
Raloxifene 15.7 5.4 0.44 N.A.
Zidovudine
0.8
4.8
0.78
0.85
  • N.D., data not obtained in vitro; N.A., fmUGT was not available from renal excretion data.

  • a In vitro fmUGT was calculated using eq. 5. The fmUGT estimate obtained in the absence of BSA is shown in Table 1.

  • b In vivo fmUGT values were estimated from renal excretion data.