Subject | Race | Exon 1 | Intron 1 | Exon 2 | Intron 2 | Intron 2/ Exon 3 | Intron 3 | Exon 4 | Intron 4 | Exon 5 | Exon 6 | Dosea | Cmax/Dosea | AUC/Dosea | ||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
rs61749966 | rs61749973 | rs61750900 | rs294777 | rs9917968 | rs861340 | r s2942857 | rs146889061 | rs61301802 | rs17146894 | rs75808313 | rs71616905 | rs147368959 | rs76198256 | |||||
Silent | Silent | Asp67Tyr | Intronic | Silent | Intronic | Splice Site | Intronic | Silent | Intronic | Intronic | Silent | Ile493Thy | 3′-UTR | |||||
mg | ng/ml per mg | h⋅ng/ml per mg | ||||||||||||||||
1001 | W | TT | AA | GG | GG | TT | AG | AC | GG | CC | AA | TT | TT | TT | GG | 3 | 0.036 | 0.018 |
1002 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 10/60 | 0.026/0.10 | 0.11/0.65 |
1003 | W | TT | AA | GG | GG | TT | AG | AA | GG | CC | AA | TT | CT | TT | GG | 30/125 | 0.023/0.080 | 0.071/0.20 |
1004 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 1/60 | 0.28/0.14 | 0.19/0.32 |
1005 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 30/125 | 0.026/0.26 | 0.14/0.81 |
1006 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 1/60 | BLQ/0.041 | BLQ/0.16 |
1007 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AC | AT | TT | TT | GG | 30/125 | 0.091/0.23 | 0.27/0.70 |
1008b | B | TT | AC | GG | GG | TT | GG | CC | GG | CC | AA | TT | TT | TT | GG | 10/15 | 1.15/1.55 | 35/35 |
1009 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 1/10 | 0.24/0.056 | 0.059/0.12 |
1010 | B | TT | AA | GG | AG | TT | AG | AC | GG | CC | AA | TT | TT | TT | GG | 1/10 | BLQ/0.060 | BLQ/0.34 |
1011 | B | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | CT | GG | 0 | — | — |
1012 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 3/30 | 0.057/0.26 | 0.086/0.11 |
1013 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 3/125 | 0.077/0.98 | 0.29/2.9 |
1014 | B | TT | AA | GG | AG | TT | AG | AC | GG | CC | AA | TT | TT | TT | GG | 1/10 | 0.27/0.069 | 0.45/0.30 |
1015 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AC | AT | TT | TT | GG | 3/125 | 0.043/0.43 | 0.032/1.1 |
1016 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 3/30 | 0.073/0.16 | 0.21/0.82 |
1017 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 10/60 | 0.055/0.15 | 0.14/0.49 |
1018 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 3/30 | 0.11/0.28 | 0.34/0.70 |
1019b | B | TT | AA | GG | AG | TT | GG | CC | GG | CC | AA | TT | TT | TT | GG | 5 | 1.28 | 5.48c |
1020 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5 | 0.038 | 0.019c |
1021 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5 | 0.034 | 0.017c |
1022 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 5 | 0.078 | 0.30c |
1023 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5 | BLQ | BLQc |
1024 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 5 | 0.067 | 0.30c |
1025 | B | TT | AA | GG | GG | TT | GG | AA | GG | CC | AA | TT | TT | TT | GG | 5 | 0.36 | 1.33c |
1026 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 5 | 0.093 | 0.34c |
1027 | W | TT | AA | GG | GG | CC | GG | AA | GG | GG | AA | TT | TT | TT | GG | 5 | 0.021 | 0.011c |
1028 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/125 | 0.036/0.69 | 0.074c/1.8 |
1029 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5 | 0.028 | 0.014c |
1030 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 5/125 | 0.057/2.72 | 0.26c/5.3 |
1031 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/125 | 0.048/0.12 | 0.095c/0.61 |
1032 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 5 | 0.19 | 0.80c |
1033 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5 | 0.038 | 0.019c |
1034 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/125 | BLQ/0.91 | BLQc/1.78 |
1035 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5 | 0.029 | 0.015c |
1036b | B | TT | AA | GG | AA | TT | GG | CC | GG | CC | AA | TT | TT | TT | GG | 5 | 1.4 | 6.2c |
2001 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60 | BLQ/0.022 | BLQc/0.12 |
2002 | B | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | CT | GG | 5/60/60 | BLQ/0.23/0.56 | BLQc/0.67/0.41 |
2003 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | BLQ/0.013/0.012 | BLQc/0.077/0.093 |
2004 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | 0.033/0.066/0.25 | 0.017c/0.19/0.12 |
2005 | W | CT | AA | GT | GG | TT | AG | AA | GT | CC | AA | TT | TT | TT | AG | 5/60/60 | 0.038/0.10/0.28 | 0.17c/0.60/0.99 |
2006 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | BLQ/0.16/0.028 | BLQc/0.97/0.12 |
2007 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | BLQ/0.68/0.022 | BLQc/0.22/0.13 |
2008 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | BLQ/0.011/0.16 | BLQc/0.072/0.091 |
2009 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | BLQ/0.037/0.024 | BLQc/0.20/0.20 |
2010 | W | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | BLQ/0.024/0.14 | BLQc/0.14/0.076 |
2011 | W | TT | AA | GG | AG | CT | GG | AC | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | 0.044/0.62/0.15 | 0.11c/2.2/0.84 |
2012 | B | TT | AA | GG | GG | TT | AA | AA | GG | CC | AA | TT | TT | TT | GG | 5/60/60 | 0.053/0.031/0.26 | 0.11c/0.18/0.21 |
3′-UTR, 3′-untranslated region; AUC, area under the curve; B, black; BLQ, below limit of quantification; W, white.
↵a Each subject received one placebo and two active doses between 1 mg and 125 mg in a randomized manner, in fasted state. 5/60/60 indicates that after the probe dose of 5 mg, subjects received 60 mg once in the fasted state and once in the fed state.
↵b RO5263397 poor metabolizers.
↵c AUClast 0–6 hours postdose for probe dose of 5 mg.