Gene Polymorphisms Play an Important Role in the Drug Interaction Between Posaconazole and Tacrolimus in Renal Transplant Patients.

BACKGROUND

Posaconazole (POSA), a second-generation triazole antifungal drug, inhibits CYP3A and P-glycoprotein. Here, the interaction between POSA and tacrolimus (TAC) in patients undergoing early renal transplantation was studied.

METHODS

Twenty-two renal transplant recipients who received POSA as antifungal therapy were studied. The following indicators were analyzed statistically: the blood concentration (C), dose (D), and concentration-dose ratio (C/D) of TAC before and after introducing POSA; the change of C/D (ΔC/D) after starting POSA; the genotypes of CYP3A5*3, ABCB1 3435, ABCB1 1236, and POR*28; other routine clinical indicators.

RESULTS

After starting POSA, the C, D, and C/D values of TAC were 1.29, 0.57, and 2.74 times the original values, respectively. A linear correlation was observed between the plasma levels of POSA and ΔC/D. The CYP3A5*3 gene polymorphism showed a significant impact on C, D, and C/D of TAC; however, it did not affect the ΔC/D. Polymorphism of the ABCB1 3435 gene had a significant effect on ΔC/D, and patients with the CC genotype in ABCB1 3435 had significantly lower ΔC/D than the CT/TT patients.

CONCLUSIONS

In renal transplant patients, considerable interindividual variability was observed in the drug interactions between POSA and TAC. The genotypes of CYP3A5*3 and ABCB1 3435 and the plasma level of POSA had strong impact on the interaction between POSA and TAC.