Prediction of the increase in midazolam AUC assuming a competitive inhibition of CYP3A by erythromycin or clarithromycin
Imax | ka D Fa/Q | Iin,ua | Ki b | Predicted AUC Ratioc | |
|---|---|---|---|---|---|
| μM | μM | μM | μM | ||
| Erythromycin (500 mg p.o.) | 3.72 | 2.70 | 1.03 | 148 | 1.01 |
| Clarithromycin (250 mg p.o.) | 0.99 | 3.74 | 1.32 | 330 | 1.00 |
|
Clarithromycin (500 mg p.o.)
|
1.98
|
7.47
|
2.65
|
330
|
1.01
|
↵ a Iin,u = (Imax + ka D Fa/Q) × fu, where Imax is maximum systemic concentration, ka is absorption rate constant, D is dose, Fa is fraction absorbed, Q is hepatic blood flow, and fu is unbound fraction.
↵ b Ki or IC50 for the inhibition of midazolam α-hydroxylation by human liver microsomes (Gascon and Dayer, 1991).
↵ c Predicted AUC ratio = 1 + Iin,u/Ki.