Effect of Genetic Polymorphism of CYP3A5 and CYP2C19 and Concomitant Use of Voriconazole on Blood Tacrolimus Concentration in Patients Receiving Hematopoietic Stem Cell Transplantation

Abstract

In HSCT recipients, the variability of intravenous TAC concentration in the blood could be explained in part by the genetic variation of CYP3A5. The study results also strongly imply that the magnitude of hepatic interaction between TAC and VRCZ is affected by the genetic polymorphism of both CYP3A5 and CYP2C19 genes.

Population pharmacokinetics of voriconazole and CYP2C19 polymorphisms for optimizing dosing regimens in renal transplant recipients

“…The strong inhibition of CYP3A4 by VRC in the small intestine and liver is likely to be the main mechanism of these DDIs. The magnitude of the interaction between VRC and tacrolimus was found to be affected by CYP3A5 polymorphisms as well as by CYP2C19 polymorphisms that result in different VRC exposure . It was shown that VRC could increase intracellular cyclosporine concentrations via inhibiting the P‐glycoprotein‐mediated transport of cyclosporine .…”

Drug-interactions of azole antifungals with selected immunosuppressants in transplant patients: strategies for optimal management in clinical practice

“…These polymorphisms can also influence the magnitude of DDIs between azoles and immunosuppressants [11,12]. The details of the interplay between DDIs and genetic variability in metabolizing enzymes are beyond the scope of this review and will not be further discussed.…”

Evaluation of the interaction of intravenous and oral voriconazole with oral cyclosporine in iranian HSCT patients

“…found that the magnitude of CsA level increment did not correlate with plasma concentrations of oral voriconazole. [711] We identified a significant correlation between trough plasma concentration of voriconazole and the increase in the CsA C/D ratio in Iranian population, and our results suggest that the magnitude of drug interaction between CsA and voriconazole is affected by the plasma concentration of voriconazole. However, after subanalysis it was found that this correlation did not exist in patients who received voriconazole orally as has been demonstrated previously in Japanese population.…”

“…However, after subanalysis it was found that this correlation did not exist in patients who received voriconazole orally as has been demonstrated previously in Japanese population. [711] Genetic polymorphism of CYP3A4, CYP3A5, and CYP3A7 seems to be a relevant reason for this absence of correlation. [1213] In patients received voriconazole orally, both hepatic and GI CYP heterogeneity may be contributed to this wide variability.…”