Trial reportEuropean journal of clinical pharmacology2013
Effect of the P450 oxidoreductase 28 polymorphism on the pharmacokinetics of tacrolimus in Chinese healthy male volunteers.
Trial report in European journal of clinical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 59 citations in OpenAlex.
- A preliminary exploration of liver microsomes and PBPK to uncover the impact of CYP3A4/5 and CYP2C19 on tacrolimus and voriconazole drug-drug interactions.Scientific reports · 2025Article
- A descriptive study of the single-nucleotide polymorphisms known to affect the Tacrolimus trough concentration per dose, among a population of kidney failure patients in a tertiary hospital in Ghana.BMC research notes · 2024Article
- Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics.Advances in pharmacological and pharmaceutical sciences · 2024Review
- Improving prediction of tacrolimus concentration using a combination of population pharmacokinetic modeling and machine learning in chinese renal transplant recipients.Frontiers in pharmacology · 2024Article
- Genotypic and phenotypic landscapes of 51 pharmacogenes derived from whole-genome sequencing in a Thai population.PloS one · 2022Article
- Avoiding Tacrolimus Underexposure and Overexposure with a Dosing Algorithm for Renal Transplant Recipients: A Single Arm Prospective Intervention Trial.Clinical pharmacology and therapeutics · 2021Article
- Investigation of the Impact ofPharmaceuticals (Basel, Switzerland) · 2021Article
- Population pharmacokinetic analysis of tacrolimus in Chinese cardiac transplant recipients.European journal of hospital pharmacy : science and practice · 2020Article
- CYP3A5 and CYP3A7 genetic polymorphisms affect tacrolimus concentration in pediatric patients with nephrotic range proteinuria.European journal of clinical pharmacology · 2019Article
- Impact ofInternational journal of molecular sciences · 2019Article
- Pharmacokinetics, Pharmacodynamics and Pharmacogenetics of Tacrolimus in Kidney Transplantation.Current drug metabolism · 2018Review
- CYP3A5 polymorphisms in renal transplant recipients: influence on tacrolimus treatment.Pharmacogenomics and personalized medicine · 2018Review
- Theory-based pharmacokinetics and pharmacodynamics of S- and R-warfarin and effects on international normalized ratio: influence of body size, composition and genotype in cardiac surgery patients.British journal of clinical pharmacology · 2017Article
- Associations of cytochrome P450 oxidoreductase genetic polymorphisms with smoking cessation in a Chinese population.Human genetics · 2016Article
- The POR rs1057868-rs2868177 GC-GT diplotype is associated with high tacrolimus concentrations in early post-renal transplant recipients.Acta pharmacologica Sinica · 2016Article
- Multigene predictors of tacrolimus exposure in kidney transplant recipients.Pharmacogenomics · 2015Article
- Pharmacogenomics and personalized medicine: a review focused on their application in the Chinese population.Acta pharmacologica Sinica · 2015Review
- Cytochrome P450 Oxidoreductase Influences CYP2B6 Activity in Cyclophosphamide Bioactivation.PloS one · 2015Article
- Role of pharmacogenomics in dialysis and transplantation.Current opinion in nephrology and hypertension · 2014Article
- Lack of association of the p450 oxidoreductase *28 single nucleotide polymorphism with the lipid-lowering effect of statins in hypercholesterolemic patients.Molecular diagnosis & therapy · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeTo assess the influence of the P450 oxidoreductase 28 SNP (POR 28) on tacrolimus pharmacokinetics in the Chinese population.
methodsSeventy-one healthy Chinese volunteers enrolled in the study received an oral dose of 2 mg of tacrolimus after providing written informed consent. CYP3A5 3 was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and POR*28 was genotyped by PCR-direct sequencing. Tacrolimus whole blood concentrations were determined by ultra performance liquid chromatography-tandem mass spectrometry and the pharmacokinetics analyses was evaluated by nonparametric methods.
resultsThe frequencies of CYP3A5 3 and POR 28 allele were 73.3 % and 29.6 %, respectively. No significant differences existed in tacrolimus pharmacokinetics between the POR 28 CC homozygotes (n = 32) and the POR 28 T allele (n = 39) in all subjects. The mean tacrolimus AUC0-24, AUC0-∞ and Cmax for the POR 28 CC (n = 14) homozygotes in CYP3A5 expressers (CYP3A5 1/ 1 or 1/ 3 genotype) were 71.5 ± 38.9 h ng/mL, 94.3 ± 58.3 h ng/mL and 17.6 ± 9.8 ng/mL, which were much higher than the POR 28 CT heterozygotes (n = 17) of 46.7 ± 24.9 h ng/mL, 57.4 ± 33.9 h ng/mL and 11.2 ± 6.4 ng/mL (P < 0.05, respectively). We did not observe any significant differences in tacrolimus pharmacokinetics between the POR 28 CC homozygotes (n = 18) and POR 28 T carriers (n = 22) in CYP3A5 nonexpressers (CYP3A5 3/ 3 carriers).
conclusionsThe POR 28 CT genotype presented a significantly lower level of tacrolimus exposure (AUC, Cmax) compared with the POR 28 CC genotype in CYP3A5-expressing subjects. It suggested that the POR 28 genetic polymorphism might also be responsible for the marked interindividual variability of tacrolimus besides the CYP3A5 3 genetic polymorphism.
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