Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies
Abstract Purpose This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus. Methods Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Em...
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| Format: | Article |
| Language: | English |
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BMC
2024-02-01
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| Series: | BMC Nephrology |
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| Online Access: | https://doi.org/10.1186/s12882-024-03467-4 |
| _version_ | 1797275579372797952 |
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| author | Ze Li Xiaozhen Wang Dandan Li Sheng Cheng Zhe Li Heng Guo Yiwen Dong Yingming Zheng Xingang Li |
| author_facet | Ze Li Xiaozhen Wang Dandan Li Sheng Cheng Zhe Li Heng Guo Yiwen Dong Yingming Zheng Xingang Li |
| author_sort | Ze Li |
| collection | DOAJ |
| description | Abstract Purpose This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus. Methods Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C0/Dose). Results The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C0/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43). Conclusions CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations. |
| first_indexed | 2024-03-07T15:15:32Z |
| format | Article |
| id | doaj.art-dbd52a3e554f47ee8280b6a397a20f2f |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-03-07T15:15:32Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-dbd52a3e554f47ee8280b6a397a20f2f2024-03-05T17:57:06ZengBMCBMC Nephrology1471-23692024-02-0125111010.1186/s12882-024-03467-4Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studiesZe Li0Xiaozhen Wang1Dandan Li2Sheng Cheng3Zhe Li4Heng Guo5Yiwen Dong6Yingming Zheng7Xingang Li8Department of Pharmacy, Beijing Friendship Hospital, Capital Medical UniversityCentral Laboratory, Xuanwu Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical UniversityDepartment of Pharmacy, Beijing Friendship Hospital, Capital Medical UniversityAbstract Purpose This study aimed to investigate the association between cytochrome P450 (CYP) 3A4*22 and cytochrome P450 oxidoreductase (POR)*28 variations and the pharmacokinetics of tacrolimus. Methods Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science (SCI), MEDLINE, and Embase were systematically searched from inception to August 2022. The outcomes were weight-adjusted daily dose and dose-adjusted trough concentration (C0/Dose). Results The study included 2931 renal transplant recipients from 18 publications. Weight-adjusted daily dose of CYP3A4*1/*1 carriers was 0.04 (WMD = 0.04, 95% CI: 0.02 to 0.06), 0.03 (WMD = 0.03, 95% CI: 0.02 to 0.05), 0.02 (WMD = 0.02, 95% CI: 0.01 to 0.03), or 0.02 mg/kg/day (WMD = 0.02, 95% CI: 0.00 to 0.04) higher than CYP3A4*22 carriers in Caucasians at 1 month, 3 months, 6 months, or 12 months post-transplantation. Conversely, C0/Dose was lower for CYP3A4*1/*1 carriers at 3 days (SMD = -0.35, 95% CI: -0.65 to -0.06), 1 month (SMD = -0.67, 95% CI: -1.16 to -0.18), 3 months (SMD = -0.60, 95% CI: -0.89 to -0.31), 6 months (SMD = -0.76, 95% CI: -1.49 to -0.04), or 12 months post-transplantation (SMD = -0.69, 95% CI: -1.37 to 0.00). Furthermore, C0/Dose of POR*1/*1 carriers was 22.64 (WMD = 22.64, 95% CI: 2.54 to 42.74) or 19.41 (ng/ml)/(mg/kg/day) (WMD = 19.41, 95% CI: 9.58 to 29.24) higher than POR*28 carriers in CYP3A5 expressers at 3 days or 7 days post-transplantation, and higher in Asians at 6 months post-transplantation (SMD = 0.96, 95% CI: 0.50 to 1.43). Conclusions CYP3A4*22 variant in Caucasians restrains the metabolism of tacrolimus, while POR*28 variant in CYP3A5 expressers enhances the metabolism of tacrolimus for renal transplant recipients. However, further well-designed prospective studies are necessary to substantiate these conclusions given some limitations.https://doi.org/10.1186/s12882-024-03467-4Meta-analysisGenetic polymorphismsTacrolimusPharmacokineticsRenal transplant recipients |
| spellingShingle | Ze Li Xiaozhen Wang Dandan Li Sheng Cheng Zhe Li Heng Guo Yiwen Dong Yingming Zheng Xingang Li Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies BMC Nephrology Meta-analysis Genetic polymorphisms Tacrolimus Pharmacokinetics Renal transplant recipients |
| title | Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies |
| title_full | Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies |
| title_fullStr | Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies |
| title_full_unstemmed | Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies |
| title_short | Effects of CYP3A4*22 and POR*28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients: a meta-analysis of 18 observational studies |
| title_sort | effects of cyp3a4 22 and por 28 variations on the pharmacokinetics of tacrolimus in renal transplant recipients a meta analysis of 18 observational studies |
| topic | Meta-analysis Genetic polymorphisms Tacrolimus Pharmacokinetics Renal transplant recipients |
| url | https://doi.org/10.1186/s12882-024-03467-4 |
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