Impact of POR*28 on the Pharmacokinetics of Tacrolimus and Cyclosporine A in Renal Transplant Patients

Abstract

Our results show that the POR*28 allele is associated with increased in vivo CYP3A5 activity for Tac in CYP3A5 expressers, whereas POR*28 homozygosity was associated with a significant higher CYP3A4 activity in CYP3A5 nonexpressers for both Tac and CsA.

Pharmacogenetic aspects of the use of tacrolimus in renal transplantation: recent developments and ethnic considerations

“…[45] In a study in 71 healthy Chinese volunteers, Zhang et al [46] demonstrated that CYP3A5 expressers carrying the POR*28 variant allele had a Tac exposure that was about 40% lower than CYP3A5 expressers with wildtype POR. The increased Tac dose requirement of CYP3A5-expressing kidney transplant recipients carrying the POR*28 (T) variant allele was recently confirmed by Elens and Lunde et al [47,48] Taken together, these studies suggest that the POR*28 SNP leads to increased CYP3A5-mediated Tac metabolism, possibly resulting from a facilitated interaction between POR, CYP3A5, and Tac. In CYP3A5 non-expressers, Tac metabolism depends entirely on CYP3A4 and POR*28 apparently does not influence CYP3A4 activity to a clinically relevant degree.…”

A Lack of Significant Effect of POR*28 Allelic Variant on Tacrolimus Exposure in Kidney Transplant Recipients

“…However, the strength of this association seems weak, 19,23 and the impact of POR*28 on Tac doses requirements is limited (15%-20%), compared with those mediated by CYP3A5 and CYP3A4 variants. 21,23 Whether POR genotyping should be integrated in routine pharmacogenetic screening before Tac introduction in solid organ transplantation is not established, and the definite proof on the clinical impact of this polymorphism remains to be validated by independent large-scale studies.…”

Biomarkers for atopic dermatitis

“…123 Studies in renal transplant patients showed that the presence of SNPs in CYP3A4 and CYP3A5 influences blood levels of CsA. 124 Pharmacoge-netic testing of SNPs in CYP3A4 and CYP3A5 may also be of use in the treatment of patients with CsA and needs further investigation.…”