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Association of P450 Oxidoreductase Gene Polymorphism with Tacrolimus Pharmacokinetics in Renal Transplant Recipients: A Systematic Review and Meta-Analysis
| Content Provider | MDPI |
|---|---|
| Author | Lee, Da-Hoon Lee, Hana Yoon, Ha-Young Yee, Jeong Gwak, Hye-Sun |
| Copyright Year | 2022 |
| Description | There are conflicting results regarding the effect of the P450 oxidoreductase (POR) *28 genotype on the tacrolimus (TAC) pharmacokinetics (PKs) during the early post-transplantation period in adult renal transplant recipients. Thus, we characterized the impact of POR*28 on TAC PKs. We conducted a systematic review on the association between POR*28 and PKs of TAC in adult renal transplant recipients. Structured searches were conducted using PubMed, Web of Science, and Embase. TAC standardized trough concentration (ng/mL per mg/kg) data were extracted. Mean differences (MD) and their corresponding 95% confidence intervals (CIs) were used to identify the differences between the POR*28 genotype and PKs of TAC. The subgroup analysis was conducted according to CYP3A5 expression status. Six studies (n = 1061) were included. TAC standardized trough concentrations were significantly lower in recipients with the POR*28 allele compared to recipients with POR*1/*1 (MD: 8.30 ng/mL per mg/kg; 95% CI: 1.93, 14.67; p = 0.01). In the subgroup analysis, TAC standardized trough concentrations were lower for subjects who were POR*28 carriers than those who were POR*1/*1 in CYP3A5 expressers (MD: 20.21 ng/mL per mg/kg; 95% CI: 16.85, 23.56; p < 0.00001). No significant difference between POR*28 carriers and POR*1/*1 was found in the CYP3A5 non-expressers. The results of our meta-analysis demonstrated a definite correlation between the POR*28 genotype and PKs of TAC. Patients carrying the POR*28 allele may require a higher dose of TAC to achieve target levels compared to those with POR*1/*1, especially in CYP3A5 expressers. |
| Starting Page | 261 |
| e-ISSN | 19994923 |
| DOI | 10.3390/pharmaceutics14020261 |
| Journal | Pharmaceutics |
| Issue Number | 2 |
| Volume Number | 14 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2022-01-22 |
| Access Restriction | Open |
| Subject Keyword | Pharmaceutics Transplantation Tacrolimus Por Pharmacokinetics Kidney Transplant |
| Content Type | Text |
| Resource Type | Article |
