Table 4 Summary of the distribution of the required TAC weight-adjusted doses, after stratification on CYP3A5 genotype and GRWR classes. CYP3A5 *1/*3 was coded as 1 while *3/*3 was coded as 2. GRWR was coded as percentage.
Donor CYP3A5 genotype | GRWR | TAC weight-adjusted dose (mg/Kg/day) | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 0 | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 7 | Day 8 | Day 9 | Day 10 | Day 11 | Day 12 | Day 13 | Day 14 | Day 15 | ||||
*1/*3 | Normal | N | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | 8 | |
Quartiles | 1° | 0.036 | 0.1 | 0.102 | 0.131 | 0.159 | 0.147 | 0.113 | 0.152 | 0.2 | 0.207 | 0 | 0 | 0.156 | 0.14 | 0.166 | 0.166 | ||
2° | 0.052 | 0.137 | 0.138 | 0.194 | 0.189 | 0.198 | 0.169 | 0.185 | 0.216 | 0.241 | 0.158 | 0.14 | 0.25 | 0.3 | 0.3 | 0.3 | |||
3° | 0.109 | 0.246 | 0.294 | 0.266 | 0.224 | 0.256 | 0.224 | 0.354 | 0.258 | 0.306 | 0.263 | 0.262 | 0.298 | 0.323 | 0.323 | 0.323 | |||
Large | N | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | ||
Quartiles | 1° | 0.039 | 0.046 | 0.069 | 0.098 | 0.116 | 0.116 | 0.105 | 0.123 | 0.138 | 0.173 | 0.203 | 0.267 | 0.12 | 0.12 | 0.143 | 0.143 | ||
2° | 0.053 | 0.073 | 0.098 | 0.18 | 0.16 | 0.176 | 0.137 | 0.144 | 0.177 | 0.216 | 0.236 | 0.274 | 0.267 | 0.267 | 0.32 | 0.32 | |||
3° | 0.117 | 0.22 | 0.18 | 0.25 | 0.25 | 0.308 | 0.188 | 0.188 | 0.25 | 0.31 | 0.31 | 0.32 | 0.32 | 0.32 | 0.384 | 0.384 | |||
Extra-large | N | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | ||
Quartiles | 1° | 0.067 | 0.067 | 0.133 | 0.133 | 0.089 | 0.089 | 0.089 | 0.089 | 0.089 | 0.179 | 0.089 | 0.089 | 0.089 | 0.467 | 0.179 | 0.179 | ||
2° | 0.078 | 0.123 | 0.156 | 0.156 | 0.145 | 0.2 | 0.167 | 0.211 | 0.133 | 0.256 | 0.278 | 0.278 | 0.278 | 0.467 | 0.323 | 0.533 | |||
3° | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | |||
*3/*3 | Normal | N | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | 11 | |
Quartiles | 1° | 0.045 | 0.05 | 0.052 | 0.045 | 0.05 | 0.05 | 0.05 | 0.061 | 0.05 | 0.05 | 0 | 0.094 | 0.051 | 0.076 | 0.105 | 0.105 | ||
2° | 0.052 | 0.089 | 0.075 | 0.063 | 0.053 | 0.061 | 0.067 | 0.098 | 0.1 | 0.105 | 0.121 | 0.129 | 0.118 | 0.111 | 0.145 | 0.143 | |||
3° | 0.105 | 0.133 | 0.115 | 0.11 | 0.1 | 0.085 | 0.121 | 0.138 | 0.134 | 0.138 | 0.134 | 0.159 | 0.139 | 0.143 | 0.167 | 0.157 | |||
Large | N | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | 17 | ||
Quartiles | 1° | 0.053 | 0.057 | 0.058 | 0.058 | 0.078 | 0.073 | 0.059 | 0.086 | 0.097 | 0.08 | 0.07 | 0.072 | 0.06 | 0.058 | 0.072 | 0.078 | ||
2° | 0.06 | 0.085 | 0.064 | 0.065 | 0.091 | 0.118 | 0.136 | 0.126 | 0.188 | 0.195 | 0.174 | 0.179 | 0.122 | 0.126 | 0.187 | 0.16 | |||
3° | 0.08 | 0.145 | 0.083 | 0.081 | 0.132 | 0.218 | 0.197 | 0.221 | 0.282 | 0.312 | 0.379 | 0.311 | 0.235 | 0.274 | 0.268 | 0.369 | |||
Extra-large | N | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | 7 | ||
Quartiles | 1° | 0.072 | 0.035 | 0.086 | 0.163 | 0.083 | 0.136 | 0.136 | 0.126 | 0.072 | 0.094 | 0.166 | 0.126 | 0.126 | 0.215 | 0.2 | 0.09 | ||
2° | 0.082 | 0.072 | 0.109 | 0.208 | 0.152 | 0.213 | 0.213 | 0.187 | 0.146 | 0.21 | 0.224 | 0.2 | 0.221 | 0.253 | 0.23 | 0.221 | |||
3° | 0.139 | 0.157 | 0.16 | 0.259 | 0.199 | 0.245 | 0.312 | 0.221 | 0.213 | 0.221 | 0.254 | 0.326 | 0.368 | 0.293 | 0.293 | 0.301 | |||
Multivariate linear regression p values to predict weight-adjusted TAC dose (mg/kg/day) | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 7 | Day 8 | Day 9 | Day 10 | Day 11 | Day 12 | Day 13 | Day 14 | Day 15 | |||||
GRWR (Unstand. B coeff.) | 0.401 (-) | 0.714 (-) | 0.089 (0.012) | 0.161 (-) | 0.003 (0.024) | 0.078 (0.017) | 0.124 (-) | 0.224 (-) | 0.065 (0.021) | 0.006 (0.037) | 0.008 (0.03) | 0.032 (0.024) | 0.006 (0.037) | 0.046 (0.023) | 0.009 (0.039) | ||||
Donor CYP3A5 genotype (Unstand. B coeff.) | 0.092 (− 0.049) | 0.004 (− 0.089) | < .001 (− 0.086) | < .001(− 0.078) | < .001 (− 0.099) | 0.106 (-) | 0.047 (− 0.064) | 0.125 (-) | 0.012 (− 0.090) | 0.369 (-) | 0.17 (-) | 0.018 (− 0.094) | 0.01 (− 0.115) | 0.005 (− 0.117) | 0.05 (− 0.079) | ||||
Determ. Coeff. (R2) | 0.093 | 0.194 | 0.256 | 0.31 | 0.336 | 0.091 | 0.126 | 0.064 | 0.157 | 0.139 | 0.119 | 0.183 | 0.239 | 0.253 | 0.172 | ||||
F statistic (d.f. , res.) | 4.22 (1, 47) | 10.1 (1, 47) | 14.41 (1, 47) | 18.89 (1, 47) | 10,10 (2, 46) | 2.59 (2, 46) | 3.16 (2, 46) | 1.51 (2, 46) | 4.09 (2, 46) | 7.24 (1, 47) | 6.08 (1, 47) | 4.26 (2, 46) | 5.97 (2, 46) | 5.59 (2, 46) | 6.44 (1, 47) | ||||
Intercept | 0.194 | 0.268 | 0.242 | 0.261 | 0.236 | 0.084 | 0.23 | 0.168 | 0.279 | 0.052 | 0.07 | 0.255 | 0.254 | 0.334 | 0.059 |