Kinetic parameters (mean ± S.D.) of clopidogrel carboxylic acid glucuronidation by UGT1A3, UGT1A9, UGT1A10-H, UGT2B4, UGT2B7, and UGT2B17 and scaling of their contributions to the total microsomal intrinsic clearance in the liver and intestine
| UGT1A3 | UGT1A9 | UGT1A10-H | UGT2B4 | UGT2B7 | UGT2B17 | ||
|---|---|---|---|---|---|---|---|
| Model | MM | MM | MM | Two binding sites | MM | MM | |
| Vmax (pmol⋅min−1⋅mg−1) | 595 ± 28 | 61.5 ± 2.8 | 28.7 ± 1.4 | 8.57 ± 1.77 (Vmax1) 131 ± 5.97 (Vmax2) | 50.5 ± 1.7 | 511 ± 11 | |
| Km (µM) | 1980 ± 150 | 74.8 ± 14.5 | 307 ± 38 | 19.0 ± 8.50 (Km1) 2340 ± 274 (Km2) | 20.9 ± 3.2 | 181 ± 12 | |
| CLint,u (µl⋅min−1⋅mg−1) | 0.301 | 0.822 | 0.0936 | 0.451 (CLint1) 0.0560 (CLint2) | 2.42 | 2.82 | |
| Liver | |||||||
| CLint,u,HLM Satoa (µl⋅min−1⋅mg HLM−1) | 0.00380 (1.3%) | 0.0257 (9.1%) | NA | 0.0577 (20.3%) | 0.157 (55.3%) | 0.0394 (13.9%) | |
| CLint,u,HLM Fallonb (µl⋅min−1⋅mg HLM−1) | 0.00528 (1.6%) | 0.0395 (12.3%) | NA | 0.0528 (16.5%) | 0.194 (60.4%) | 0.0293 (9.1%) | |
| Intestine | |||||||
| CLint,u,HIM Satoa (µl⋅min−1⋅mg HIM−1) | 0.000380 (0.4%) | NA | 0.000740 (0.7%) | NA | 0.0126 (12.0%) | 0.0912 (87.0%) | |
MM, Michaelis-Menten; NA, not applicable.
↵a Scaling of intrinsic clearance values was calculated using UGT abundancies in the liver and intestine published by Sato et al. (2014).
↵b Scaling of intrinsic clearance values was calculated using UGT abundancies in the liver published by Fallon et al. (2013a,b).