Potential in vivo DDIs between efavirenz with drug inhibitors
Inhibitors | Estimated in Vivo Cmaxa | Predicted in Vivo Activityb | ||
|---|---|---|---|---|
| CYP2B6dH | K262R | |||
| /min | /min | |||
| NIL | 2.05 (100)c | 3.55 (100) | ||
| Clopidogrel | 9.3 | 0.04 (1.9) | 0.27 (7.6) | |
| Clotrimazole | 3.7 | 0.13 (6.3) | 0.23 (6.5) | |
| Itraconazole | 1.9 | 1.16 (57) | 2.84 (80) | |
| Raloxifene | 0.003 | 2.06 (100) | 3.55 (100) | |
| Sertraline | 0.62 | 0.99 (48) | 3.00 (84) | |
| Ticlopidine | 1.6 | 0.30 (15) | 0.47 (13) | |
↵ a Cmax of the inhibitors and substrate were obtained from the following literature sources: www.mentalhealth.com/drug/p30-z02.html (sertraline); www.medscape.com/ (raloxifene); www.pharmgkb.org/ (ticlopidine, clopidogrel, and efavirenz); Burgess and Bodey (1972) (clotrimazole); Goodwin and Drew (2008) (itraconazole).
↵ b Predicted in vivo activity was determined using the equation for competitive inhibition. The values for [S] and [I] correspond to the estimated in vivo Cmax of efavirenz (13.0 μM) and drug inhibitor, respectively. The Ki values were taken from Table 1, whereas kcat and Km values were taken from a previous study (Bumpus et al., 2006). Predicted activities for K262R assume that both CYP2B6 alleles are the variant.
↵ c The values in parenthesis indicate the percentage activity.