Glucuronidation of opioids and other drugs catalyzed by expressed UGT1A8 not by UGT1A10
| Substrate | Glucuronide Formation |
|---|---|
| pmol/min/mg protein | |
| Opioids | |
| Morphine (5 mM) | 35 |
| Hydromorphone (2.5 mM) | 33 |
| Naloxone (1 mM) | 81 |
| Naltrexone (2.5 mM) | 137 |
| Nalorphine (2.5 mM) | 75 |
| Dihydromorphone (0.5 mM) | 29 |
| Buprenorphine (0.25 mM) | 28 |
| Codeine (2.5 mM) | ND |
| Other drugs | |
| Ciprofibrate | 86 |
| Clofibrate | 8 |
| Valproic acid | 10 |
| Furosemide | 53 |
| Diflunisal | 44 |
| 4-hydroxytamoxifen (0.1 mM) | 41 |
| Phenolphthalein | 123 |
| Hexafluoro-2-propanol | 8 |
| Acetaminophen | ND |
| Chloramphenicol | ND |
| R-propanolol | ND |
| S-propanolol | ND |
| Probenecid | ND |
Assays were performed using pH 7.4 Tris buffer at 37°C for 1.0 h and membrane preparations of HK293 cells expressing UGT1A8. The concentration of UDP-glucuronic acid was 2.0 mM and the aglycone concentrations were 0.5 mM or as otherwise indicated. Values represent the average enzymatic rates from two different experiments. Stably expressed human UGT1A10 showed no glucuronidation activity with any compound listed in Table 4.
ND, not detected (limit of detection is 2.0 pmol/min/mg protein).