TABLE 1

UGT2B10 genotypes versus individual dose-normalized pharmacokinetic parameters of all administered doses

SubjectRaceExon 1Intron 1Exon 2Intron 2Intron 2/ Exon 3Intron 3Exon 4Intron 4Exon 5Exon 6DoseaCmax/DoseaAUC/Dosea
rs61749966rs61749973rs61750900rs294777rs9917968rs861340r s2942857rs146889061rs61301802rs17146894rs75808313rs71616905rs147368959rs76198256
SilentSilentAsp67TyrIntronicSilentIntronicSplice SiteIntronicSilentIntronicIntronicSilentIle493Thy3′-UTR
mgng/ml per mgh⋅ng/ml per mg
1001WTTAAGGGGTTAGACGGCCAATTTTTTGG30.0360.018
1002WCTAAGTGGTTAGAAGTCCAATTTTTTAG10/600.026/0.100.11/0.65
1003WTTAAGGGGTTAGAAGGCCAATTCTTTGG30/1250.023/0.0800.071/0.20
1004WTTAAGGGGTTAAAAGGCCAATTTTTTGG1/600.28/0.140.19/0.32
1005WTTAAGGGGTTAAAAGGCCAATTTTTTGG30/1250.026/0.260.14/0.81
1006WTTAAGGGGTTAAAAGGCCAATTTTTTGG1/60BLQ/0.041BLQ/0.16
1007WTTAAGGGGTTAAAAGGCCACATTTTTGG30/1250.091/0.230.27/0.70
1008bBTTACGGGGTTGGCCGGCCAATTTTTTGG10/151.15/1.5535/35
1009WTTAAGGGGTTAAAAGGCCAATTTTTTGG1/100.24/0.0560.059/0.12
1010BTTAAGGAGTTAGACGGCCAATTTTTTGG1/10BLQ/0.060BLQ/0.34
1011BTTAAGGGGTTAAAAGGCCAATTTTCTGG0——
1012WTTAAGGGGTTAAAAGGCCAATTTTTTGG3/300.057/0.260.086/0.11
1013WCTAAGTGGTTAGAAGTCCAATTTTTTAG3/1250.077/0.980.29/2.9
1014BTTAAGGAGTTAGACGGCCAATTTTTTGG1/100.27/0.0690.45/0.30
1015WTTAAGGGGTTAAAAGGCCACATTTTTGG3/1250.043/0.430.032/1.1
1016WCTAAGTGGTTAGAAGTCCAATTTTTTAG3/300.073/0.160.21/0.82
1017WTTAAGGGGTTAAAAGGCCAATTTTTTGG10/600.055/0.150.14/0.49
1018WCTAAGTGGTTAGAAGTCCAATTTTTTAG3/300.11/0.280.34/0.70
1019bBTTAAGGAGTTGGCCGGCCAATTTTTTGG51.285.48c
1020WTTAAGGGGTTAAAAGGCCAATTTTTTGG50.0380.019c
1021WTTAAGGGGTTAAAAGGCCAATTTTTTGG50.0340.017c
1022WCTAAGTGGTTAGAAGTCCAATTTTTTAG50.0780.30c
1023WTTAAGGGGTTAAAAGGCCAATTTTTTGG5BLQBLQc
1024WCTAAGTGGTTAGAAGTCCAATTTTTTAG50.0670.30c
1025BTTAAGGGGTTGGAAGGCCAATTTTTTGG50.361.33c
1026WCTAAGTGGTTAGAAGTCCAATTTTTTAG50.0930.34c
1027WTTAAGGGGCCGGAAGGGGAATTTTTTGG50.0210.011c
1028WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/1250.036/0.690.074c/1.8
1029WTTAAGGGGTTAAAAGGCCAATTTTTTGG50.0280.014c
1030WCTAAGTGGTTAGAAGTCCAATTTTTTAG5/1250.057/2.720.26c/5.3
1031WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/1250.048/0.120.095c/0.61
1032WCTAAGTGGTTAGAAGTCCAATTTTTTAG50.190.80c
1033WTTAAGGGGTTAAAAGGCCAATTTTTTGG50.0380.019c
1034WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/125BLQ/0.91BLQc/1.78
1035WTTAAGGGGTTAAAAGGCCAATTTTTTGG50.0290.015c
1036bBTTAAGGAATTGGCCGGCCAATTTTTTGG51.46.2c
2001WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60BLQ/0.022BLQc/0.12
2002BTTAAGGGGTTAAAAGGCCAATTTTCTGG5/60/60BLQ/0.23/0.56BLQc/0.67/0.41
2003WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60/60BLQ/0.013/0.012BLQc/0.077/0.093
2004WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60/600.033/0.066/0.250.017c/0.19/0.12
2005WCTAAGTGGTTAGAAGTCCAATTTTTTAG5/60/600.038/0.10/0.280.17c/0.60/0.99
2006WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60/60BLQ/0.16/0.028BLQc/0.97/0.12
2007WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60/60BLQ/0.68/0.022BLQc/0.22/0.13
2008WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60/60BLQ/0.011/0.16BLQc/0.072/0.091
2009WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60/60BLQ/0.037/0.024BLQc/0.20/0.20
2010WTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60/60BLQ/0.024/0.14BLQc/0.14/0.076
2011WTTAAGGAGCTGGACGGCCAATTTTTTGG5/60/600.044/0.62/0.150.11c/2.2/0.84
2012BTTAAGGGGTTAAAAGGCCAATTTTTTGG5/60/600.053/0.031/0.260.11c/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.