Kidney transplant recipients carrying the CYP3A4∗22 allelic variant have reduced tacrolimus clearance and often reach supratherapeutic tacrolimus concentrations

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Abstract

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.

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APA

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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