CYP3A4∗22 is an allelic variant of the cytochrome P450 3A4 associated with a decreased activity. Carriers of this polymorphism may require reduced tacrolimus (Tac) doses to reach the target residual concentrations (Co). We tested this hypothesis in a population of kidney transplant recipients extracted from a multicenter, prospective and randomized study. Among the 186 kidney transplant recipients included, 9.3% (18 patients) were heterozygous for the CYP3A4∗22 genotype and none were homozygous (allele frequency of 4.8%). Ten days after transplantation (3 days after starting treatment with Tac), 11% of the CYP3A4∗22 carriers were within the target range of Tac Co (10-15 ng/mL), whereas among the CYP3A4∗1/∗1 carriers, 40% were within the target range (p = 0.02, OR = 0.19 [0.03; 0.69]). The mean Tac Co at day 10 in the CYP3A4∗1/∗22 group was 23.5 ng/mL (16.6-30.9) compared with 15.1 ng/mL (14-16.3) in the CYP3A4∗1/∗1 group, p < 0.001. The Tac Co/dose significantly depended on the CYP3A4 genotype during the follow-up (random effects model, p < 0.001) with the corresponding equivalent dose for patients heterozygous for CYP3A4∗22 being 0.67 [0.54; 0.84] times the dose for CYP3A4∗1/∗1 carriers. In conclusion, the CYP3A4∗22 allelic variant is associated with a significantly altered Tac metabolism and carriers of this polymorphism often reach supratherapeutic concentrations.
CITATION STYLE
Pallet, N., Jannot, A. S., El Bahri, M., Etienne, I., Buchler, M., De Ligny, B. H., … Thervet, E. (2015). Kidney transplant recipients carrying the CYP3A4∗22 allelic variant have reduced tacrolimus clearance and often reach supratherapeutic tacrolimus concentrations. American Journal of Transplantation, 15(3), 800–805. https://doi.org/10.1111/ajt.13059
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