List of inhibitor concentrations and in vitro estimates for macrolides and diltiazem used for the prediction of 37 time-dependent interactions
[I]av,ua | [I]in,ua | kinact | KI | Reference for in Vitro Data | ||
|---|---|---|---|---|---|---|
| μM | min-1 | μM | ||||
| Azithromycinb | 0.1-0.2 | 0.31-0.63 | 0.02 | 656 | Ito et al. (2003) | |
| Erythromycinb | 0.08-0.17 | 0.3-0.6 | 0.025 | 13.35 | Ito et al. (2003) | |
| Clarithromycinb | 0.14-0.28 | 1.2-2.4 | 0.044 | 39 | Ito et al. (2003) | |
| Diltiazemc,d | 0.02-0.05 | 0.33-1.3 | 0.07 | 2 | Rowland Yeo and Yeo (2001) | |
↵ a The unbound fractions to the plasma protein were 0.16, 0.7, 0.28, and 0.175 for erythromycin, clarithromycin, azithromycin, and diltiazem, respectively. The same plasma protein binding as for diltiazem and the relative plasma concentration of 38% of the parent were assumed for N-desmethyldiltiazem (Echizen and Eichelbaum, 1986).
↵ b The values represent the mean of estimates obtained for two midazolam pathways (1′ - and 4-hydroxy).
↵ c KI value corrected for the microsomal fraction unbound of 0.61 as described under Materials and Methods.
↵ d The kinact and KI for N-desmethyldiltiazem were 0.027 and 0.77, respectively (Mayhew et al., 2000).