Chemical | Mode of Inhibition | Apparent Ki | Plasma Drug Concentration [I] | R Value (1 + [I]/Ki)a | Reference for [I] Value |
---|---|---|---|---|---|
μM | μM | ||||
Galeterone | Competitive | 0.19 ± 0.07 | 2.81 | 15.79 | Kramer et al. (2013) |
Abiraterone acetate | Competitive | 0.47 ± 0.20b | 3.40c | 8.23 | Chi et al. (2015) |
0.65d | 2.38 | Han et al. (2015) | |||
0.32e | 1.68 | Acharya et al. (2012) | |||
Cyproterone acetate | Competitive (partial) | 1.24 ± 0.41 | 0.61 | 1.49 | Kuhnz et al. (1997) |
Spironolactone | Mixed (partial) | 4.63 ± 1.79 | 1.86 | 1.40 | Karim (1978) |
Danazol | Mixed (partial) | 1.90 ± 0.82 | 0.59 | 1.31 | Charman et al. (1993) |
↵a R value was calculated as 1 + [I]/Ki, where [I] represents the maximal total drug concentration in plasma. According to the US Food and Drug Administration guidelines for drug interaction studies (Food and Drug Administration, 2012), an R value of greater than 1.1 indicates potential in vivo inhibition.
↵b The temporal pattern of abiraterone formation and abiraterone acetate depletion suggested that abiraterone, not abiraterone acetate, was responsible for the inhibition of DHEA sulfonation in incubations containing human liver cytosol and abiraterone acetate (Fig. 9). Nonlinear least-squares regression analysis of enzyme kinetic data obtained from the same experiment yielded comparable apparent Ki values in incubations containing abiraterone (0.60 ± 0.09 μM) or abiraterone acetate (0.51 ± 0.20 μM).
↵c Administered after food in healthy subjects.
↵d Patients with metastatic castration-resistant prostate cancer.
↵e Healthy subjects.