Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 13 2 2023 03 19 The Impact of Single Nucleotide Polymorphisms on the Pharmacokinetics of Tacrolimus in Kidney Allograft Recipients of Northern-West, Iran 393 398 10.34172/apb.2023.038 EN Elaheh Jabbari Hagh Ali Mousavi Seyyedeh Mina Hejazian https://orcid.org/0000-0001-9154-9581 Mehdi Haghi https://orcid.org/0000-0001-8400-4209 Samaneh Esfahanian Elham Ahmadian https://orcid.org/0000-0002-7230-0489 Sepideh Zununi Vahed https://orcid.org/0000-0003-0179-4562 Mohammadreza Ardalan https://orcid.org/0000-0002-6851-5460 Journal Article 10.34172/apb.2023.038 2021 10 11 2021 12 31 Purpose: Calcineurin inhibitors (CNIs) such as tacrolimus are a major immunosuppressive therapy after renal transplantation, which inhibit cytokine expression. The pharmacokinetics of such drugs is influenced by cytochrome P450 (CYP) enzymes, multi-drug resistance-1 (MDR-1), and C25385T pregnane X receptor (PXR). This study aimed to investigate the impact of single nucleotide polymorphisms (SNP) in these genes on the ratio of tacrolimus level per drug dosage (C/D ratio), acute graft rejection, and viral infections. Methods: Kidney transplantation recipients (n=65) under similar immunosuppressive treatment were included. Amplification refractory mutation systempolymerase chain reaction (ARMS-PCR) method was applied to amplify the loci containing the SNPs of interest. Results: Overall, 65 patients with a male/female ratio of 37/28 were included. The mean age was 38±1.75 years. The variant allele frequencies of CYP3A5*3, MDR-1 C3435T, and PXR C25385T were 95.38, 20.77, and 26.92%, respectively. No significant correlations were found between the studied SNPs and the tacrolimus C/D ratios. However, there was a significant difference in the C/D ratios at 2 and 8 weeks in homozygote CYP3A5 *3/*3 carriers (P=0.015). No significant association was found between the studied polymorphisms and viral infections and acute graft rejection (P>0.05). Conclusion: Homozygote CYP3A5 *3/*3 genotype could influence the tacrolimus metabolism rate (C/D ratio).