Effect of quinidine on delavirdine desalkylation catalyzed by human liver microsomes
| Subject | CYP2D6 | DextromethorphanO-Demethylation3-a | Delavirdine Desalkylation3-a | ||
|---|---|---|---|---|---|
| Quinidine (μM) | |||||
| 0 | 1 | 10 | |||
| HL 11 | Normal | 630 | 439 | 371 (85)3-b | 360 (82)3-b |
| HL 22 | Normal | 380 | 89 | 74 (83) | 71 (80) |
| HL 24 | Normal | 280 | 75 | 59 (79) | 60 (79) |
| HL 16 | Deficient | 70 | 168 | 160 (95) | 154 (91) |
| HL 18 | Deficient | 30 | 829 | 791 (95) | 764 (92) |
| HL 19 | Deficient | 60 | 174 | 171 (98) | 167 (96) |
Microsomal protein (0.5 mg/ml) from the donors shown was incubated with delavirdine (40 μM) in the presence of quinidine at the concentrations shown. Reaction was allowed to proceed for 5 min, followed by assay of desalkyl delavirdine. Values are mean of duplicate determinations.
↵3-a Rates are pmol/min/mg protein.
↵3-b Values in parentheses represent percentage of control (no quinidine).