Article Figures & Data
Figures
- Fig. 1.
Schematic detailing AZ induction strategy from preclinical to clinical assessment.
- Fig. 2.
Plasma concentrations of 4β-hydroxycholesterol before and after 2 weeks of treatment with daily doses of 20, 100, and 500 mg rifampicin (Kanebratt et al., 2008, figure published with permission from the publisher).
- Fig. 3.
Structure of AZD1208.
- Fig. 4.
Plasma concentrations of 4β-hydroxycholesterol before and after 2 weeks of treatment with daily doses of 700 or 800 mg AZD1208.
Tables
Cell Type Maximum Concentration Tested CYP3A4 mRNA CYP3A4 Activity Observed Fold Inductiona Percentage Rifampicin Inductionb Observed Fold Induction Percentage Rifampicin Induction μM HepaRG 30 3.3 5.4 Not tested Not tested Hepatocyte lot 321 30 2.4 2.5 Concentration-dependent decrease Hepatocyte lot 349 30 3.4 1.6 Concentration-dependent decrease Hepatocyte lot 295 10 3.4 <1.0 1.1 Not calculated
Data Supplement
Files in this Data Supplement:
- Supplemental Data -
Supplemental Figure 1 - demonstrate the concordance CYP3A mRNA Emax and EC50 and efficiency ratios (Emax/EC50)...
Methods
Supplemental Table 1 - Effect of AZD1208 on CYP3A4 mRNA and CYP3A4/5 mediated testosterone 6-beta-hydroxylase activity in human hepatocytes
References
- Supplemental Data -
In this issue
Managing the Risk of CYP3A Induction in Drug Development
