Introduction:

Tacrolimus is the main component of the immunosuppressive regimen used in patients with solid organ transplants. Tacrolimus requires blood concentration monitoring due a narrow therapeutic index and large interindividual variability in its pharmacokinetics. Genetic variation, kidney function, and drug interactions all play significant roles as well. Although genetic factors influencing immunosuppressive response have been more widely studied in kidney, heart and liver transplant patients, data regarding lung transplant patients are limited. The aim of our study was to determine the relationship between the CYP3A4 polymorphism and attainment of tacrolimus steady state level in lung transplant recipients.

Methods:

Six lung transplant recipients were included. Tacrolimus doses and trough levels were collected in the first seven days post-transplantation. Total genomic DNA was extracted from buccal swabs according to manufacturer protocol (Applied Biosystems). Polymorphisms for CYP3A4*1B (g.-392A>G), CYP3A4*2 (g.15713T>C), CYP3A4*3 (c.1334T>C), CYP3A4*12 (c.1117 C>T), CYP3A4*17 (c.566 T>C), and CYP3A4*22 (15389C>T) were detected by using the TaqMan®OpenArray® allelic discrimination assay (Life Technologies). CYP3A4 polymorphisms were defined as rapid, intermediate, normal, or poor metabolizers.

Results:

The time to achieve tacrolimus steady state level ranged from 43 to 131 hours. The time correlated well with CYP3A4 polymorphisms with a Pearson's correlation co-efficient of 0.769 (p-value 0.052).

Conclusion:

Although this was a small study, the data suggest that adjusting tacrolimus dosing to patients' CYP3A4 polymorphisms may assist in individualizing the management lung transplant patients. Larger prospective studies are needed to determine genotype-based tacrolimus dosing in lung recipients.

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