Kidney Transplant Recipients Carrying the CYP3A4_22 Allelic Variant Have Reduced Tacrolimus Clearance and Often Reach Supratherapeutic Tacrolimus Concentrations
Pallet N, Jannot A-S, et alAmerican Journal of Transplantation 2015;15(3):800-5
Aims
To assess the influence of CYP3A4_22 on tacrolimus metabolism during the first 3 months after kidney transplantation by analysing the association between CY3A4_22 genotype and the proportion of patients reaching the target concentration (10–15 ng/mL) 10 days after transplantation.
Interventions
Tacrolimus at either a fixed dosage of 0.2 mg/kg/day (control group) versus a tacrolimus dosage determined by their genotype. CYP3A5 expressers received 0.3 mg/kg/day, whereas CYP3A5 non-expressers received 0.15 mg/kg/day (adapted-dose group).
Participants
The retrospective analysis was restricted to the 186 non-expressers who had a tacrolimus dosage at day 10 posttransplant.
Outcomes
The primary outcome was the proportion of patients within the target tacrolimus concentration range (10–15 ng/mL) 10 days after transplantation and whether there was a difference between expressers and non-expressers. The secondary outcome was the association CYP3A4 genotype and the tacrolimus concentration/daily dose ratio.
Follow-up
CET Conclusions
This is an interesting pharmacokinetic study examining the influence of the CYP3A4*22 allelic variant on tacrolimus clearance. Carriers of this allelic variant in this study involving 186 recipients of a renal transplant suggested that carriers of the allelic variant reach much higher TAC levels than the ideal target. This does provide further evidence that a case can be made for basing tacrolimus dosage on the genotype for the CYP3A4*22 allele and such patients would be given a lower dose of tacrolimus than those not possessingthis allelic variant.
Data analysis
Modified intention-to-treat analysis
Quality notes
Previously assessed as Thervet, E., M. A. Loriot, et al. (2010). "Optimization of Initial Tacrolimus Dose Using Pharmacogenetic Testing." Clinical Pharmacology and Therapeutics 87(6): 721-726.
Trial registration
Not reported