TABLE 2
Determination of Ki and observed fit to different inhibition models for the inhibition of CYP3A4-mediated 1-hydroxylation of midazolam by telithromycin in pooled human liver microsomes
| Inhibition Type | Rate Equation | Experiment 1 | Experiment 2 | Experiment 3 | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Ki | R2 | AICc | Ki | R2 | AICc | Ki | R2 | AICc | ||
| µM | µM | µM | ||||||||
| Competitive |  | 3.68 | 0.989 | −515 | 4.29 | 0.994 | −563 | 2.99 | 0.988 | −439 |
| Noncompetitive |  | 16.9 | 0.974 | −453 | 16.8 | 0.975 | −458 | 14.1 | 0.968 | −371 |
| Uncompetitive |  | 11.0 | 0.945 | −399 | 10.1 | 0.943 | −400 | 9.07 | 0.935 | −322 |
| Mixeda |  | 4.33 | 0.990 | −516 | 4.29 | 0.994 | −561 | 3.10 | 0.988 | −437 |
v, rate of metabolite formation.
↵a α-Value for mixed inhibition determined to be 26.9, 15.6, and 151 for experiments 1, 2 and 3, respectively.