Table 1.
Multivariable determinants of tacrolimus apparent oral clearance
MDZ model | 4β‐OHC model | ||||||
---|---|---|---|---|---|---|---|
Determinants | B value | P | R 2 | Determinants | B value | P | R 2 |
All patients (n = 147) | 0.569 | 0.525 | |||||
CYP3A5 expresser | 0.671 | <0.001 | 0.292 | CYP3A5 expresser | 0.604 | <0.001 | 0.292 |
MDZ Cl/F | 0.337 | <0.001 | 0.103 | 4β‐OHC/C | 0.304 | 0.002 | 0.032 |
Haematocrit | –3.358 | <0.001 | 0.060 | Haematocrit | –2.661 | <0.001 | 0.074 |
Weight (kg) | 0.008 | <0.001 | 0.046 | Weight (kg) | 0.012 | <0.001 | 0.050 |
Age (years) | –0.008 | 0.001 | 0.040 | Age (years) | –0.008 | 0.001 | 0.061 |
TAC QD | 0.182 | 0.003 | 0.029 | TAC QD | 0.139 | 0.026 | 0.017 |
CYP3A5 non‐expressers (n = 118) | 0.437 | 0.319 | |||||
MDZ Cl/F | 0.423 | <0.001 | 0.220 | 4β‐OHC/C | 0.357 | 0.002 | 0.063 |
Haematocrit | –3.398 | <0.001 | 0.097 | Haematocrit | –2.556 | <0.001 | 0.074 |
Weight (kg) | 0.005 | 0.029 | 0.024 | Weight (kg) | 0.012 | <0.001 | 0.083 |
Age (years) | –0.008 | 0.002 | 0.049 | Age (years) | –0.008 | 0.005 | 0.100 |
TAC QD | 0.190 | 0.005 | 0.047 | – | |||
CYP3A5 expressers (n = 29) | 0.342 | ||||||
Weight (kg) | 0.014 | 0.001 | 0.247 | ||||
Age (years) | –0.008 | 0.045 | 0.095 |
Neither MDZ Cl/F nor 4β‐OHC/C explained TAC Cl/F variability in CYP3A5 expressers
4β‐OHC/C, 4β‐hydroxycholesterol/cholesterol; CYP, cytochrome P450; MDZ Cl/F, midazolam apparent oral clearance; QD, once‐daily formulation; TAC, tacrolimus