TABLE 3.
ABCB1 haplotype associations with tacrolimus pharmacokinetics.
| Tacrolimus pharmacokinetic parameter | Wild Type Haplotypea (CGC) Association to Phenotypic Meanb [95% CI] | Variant Haplotypea and Phenotypic Meanb (95% CI) |
P-valuec | |
| Variant haplotype | Phenotypic mean (95% CI) | |||
| Study dose (mg) | 2.45 [1.74 – 3.16]* | TTT | 1.58 [0.71 – 2.45]* | 0.03 |
| CL_F (L/hr) | 20.4 [14.5 – 26.3]* | TTT | 13.99 [7.87 – 20.11]* | 0.023 |
| Clearance/LBW (L/hr/kg) | 0.48 [0.37 – 0.60]* | TTT | 0.36 [0.23 – 0.47]* | 0.022 |
| AUC* (ng.hr/ml/mg) | 80.0[68.8 – 91.1] | TTT | 92.2 [74.6 – 109.8] | 0.078 |
| AUC0–4 (ng.hr/ml/mg) | 36.59 [30.2 – 42.9] | TTT | 43.9 [33.4 – 54.4] | 0.041 |
| C max/Dose (ng/ml/mg) | 3.01[2.42 – 3.59] | TTT | 4.06[3.19 – 4.93] | 0.050 |
The phenotypic means of the wildtype haplotype (CGC) vs. phenotypic means for variant haplotype (TTT). aHaplotypes displayed at positions 1236-2677-3435. Wild-type is C-G-C. bPhenotypic mean estimated from maximum likelihood methods by THESIAS; Phenotype reported as contribution of single haplotype (one chromosome). cP value represents variant haplotype comparison to wild-type by THESIAS. ∗Sex-adjusted analysis; +race-adjusted analysis.