Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease

Jiang, Zebin; Wu, Zemin; Liu, Ruixue; Du, Qin; Fu, Xi’an; Li, Min; Kuang, Yongjun; Shen, Lin; Wu, Jianhua; Xie, Weiji; Shi, Guo‐Ming; Peng, Yaxin; Zheng, Fu-Chun

doi:10.3389/fphar.2023.1102810

Cited by 4 publications

(3 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Candidate single nucleotide polymorphisms (SNPs) were mainly selected from previously reported literature, which may potentially affect tacrolimus pharmacokinetics in solid‐organ transplantation. All SNPs and their respective genes analyzed in this study are listed in Table S1 5,8,16–30 . For genotyping, briefly, a 0.5‐mL blood sample was collected and genomic DNA was extracted from ethylenediaminetetraacetic acid‐anticoagulated peripheral blood samples using a commercially available DNA purification kit (EasyPure Blood Genomic DNA Kit, Transgene Biotech).…”

Section: Methodsmentioning

confidence: 99%

“…All SNPs and their respective genes analyzed in this study are listed in Table S1. 5,8,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] For genotyping, briefly, a 0.5-mL blood sample was collected and genomic DNA was extracted from ethylenediaminetetraacetic acid-anticoagulated peripheral blood samples using a commercially available DNA purification kit (EasyPure Blood Genomic DNA Kit, Transgene Biotech). All samples with a call rate greater than 95% were genotyped using an Infinium Asian Screening Array-China Health Industry Alliance Bead chip (Illumina, Inc.) according to the Illumina Infinium HTS chip standard operating procedures.…”

Section: Genotypingmentioning

confidence: 99%

See 1 more Smart Citation

Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

Du,

Wang,

Zhang

et al. 2024

The Journal of Clinical Pharma

View full text Add to dashboard Cite

The determination of the appropriate initial dose for tacrolimus is crucial in achieving the target concentration promptly and avoiding adverse effects and poor prognosis. However, the trial‐and‐error approach is still common practice. This study aimed to establish a prediction model for an initial dosing algorithm of tacrolimus in patients receiving a lung transplant. A total of 210 lung transplant recipients were enrolled, and 26 single nucleotide polymorphisms (SNP) from 18 genes that could potentially affect tacrolimus pharmacokinetics were genotyped. Associations between SNPs and tacrolimus concentration/dose ratio were analyzed. SNPs that remained significant in pharmacogenomic analysis were further combined with clinical factors to construct a prediction model for tacrolimus initial dose. The dose needed to reach steady state tacrolimus concentrations and achieve the target range was used to validate model prediction efficiency. Our final model consisted of 7 predictors—CYP3A5 rs776746, SLCO1B3 rs4149117, SLC2A2 rs1499821, NFATc4 rs1955915, alanine aminotransferase, direct bilirubin, and hematocrit—and explained 41.4% variance in the tacrolimus concentration/dose ratio. It achieved an area under the receiver operating characteristic curve of 0.804 (95% confidence interval, 0.746‐0.861). The Hosmer‐Lemeshow test yielded a nonsignificant P value of .790, suggesting good fit of the model. The predicted dose exhibited good correlation with the observed dose in the early postoperative period (r = 0.748, P less than .001). Our study provided a genotype‐guided prediction model for tacrolimus initial dose, which may help to guide individualized dosing of tacrolimus in the lung transplant population in clinical practice.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Genotypingmentioning

confidence: 99%

Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

Du,

Wang,

Zhang

et al. 2024

The Journal of Clinical Pharma

View full text Add to dashboard Cite

show abstract

“…Data from in vitro studies have reported that CYP3A4 and CYP3A5 were responsible for 85% and 15% of atorvastatin metabolism, respectively [8,14]. AC is first transformed into its lactone form and subsequently into two pharmacologically active metabolites (2-hydroxyatorvastatin and 4-hydroxy-atorvastatin) by these enzymes [3,15]. Aside from metabolic enzymes, AC also heavily rely on drug transporter proteins for its disposition and efficacy [3,6].…”

Section: Introductionmentioning

confidence: 99%

The Chinese-Han Population Carrying Wild-type Genotypes of SLCO1B1 388A>G, SLCO1B1 521T>C, CYP3A4 1B, CYP3A4 1G, and CYP3A5*3 Exhibits a Significant Alteration in the Pharmacokinetics of Atorvastatin Calcium

Xia,

Liu,

et al. 2023

J. Pharm. Res. Int.

View full text Add to dashboard Cite

Due to the diverse genetic characteristics of metabolism and high drug plasma exposure, great inter-subject variability exists in the clinical efficacy and incidence of adverse events. This study aimed to evaluate the associations between the SLCO1B1 388A＞G (rs2306283) polymorphism and the pharmacokinetics of atorvastatin calcium (AC) in healthy volunteers who carried the wild genotypes of SLCO1B1 521T＞C (rs4149056), CYP3A4 1B (rs2740574), CYP3A4 1G (rs2242480), and CYP3A5*3 (rs776746). A FISH technique was employed to investigate the genetic polymorphisms in 187 healthy male volunteers. The pharmacokinetic study was conducted on a group of healthy male Chinese-Han volunteers with wild-type genotypes of SLCO1B1 521T>C, CYP3A4 1B, CYP3A41G and CYP3A53 genes, consisting of either mutant heterozygotes (n=10) or mutant homozygotes (n=10) of SLCO1B1 388A>G. The results were then compared to the pharmacokinetic parameters of AC in subjects with the wild-type genotype of SLCO1B1 388A>G, as previously described. Based on the distribution of genotypes, the 187 volunteers could be divided into 28 groups. The top 10 groups accounted for nearly 85% of the total volunteers. No significant differences (P>0.05) were observed in the pharmacokinetic parameters between subjects carrying homozygous and heterozygous genotypes of SLCO1B1 388A>G. However, The Cmax of subjects carrying the wild-type genotype of SLCO1B1 388A＞G was about 14.75 times higher than that of the heterozygous genotype group and 10.43 times higher than that of the homozygous genotype group. The AUC0-72h of volunteers with the wild-type genotype of SLCO1B1 388A＞G was about 13.81 times higher than that of the heterozygous genotype group and 11.96 times higher than that of the homozygous genotype group. Volunteers carrying wild genotypes of SLCO1B1 388A＞G, SLCO1B1 521T＞C, CYP3A4 1B, CYP3A4 1G, and CYP3A5*3 showed significantly higher levels of Cmax and AUC (P<0.01), as well as markedly decreased values of CLz/F and Vz/F (P<0.01) of AC. In conclusion, patients carrying the wild genotype of SLCO1B1 388A>G, SLCO1B1 521T>C, CYP3A41G, CYP3A41B, and CYP3A5*3 should receive a lower dose of AC to minimize the risk of adverse effects.

show abstract

When the same treatment has different response: The role of pharmacogenomics in statin therapy

Zheng,

Madura,

Grandos

et al. 2024

Biomedicine & Pharmacotherapy

View full text Add to dashboard Cite

Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease

Cited by 4 publications

References 72 publications

Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

Genotype‐Guided Model for Prediction of Tacrolimus Initial Dosing After Lung Transplantation

The Chinese-Han Population Carrying Wild-type Genotypes of SLCO1B1 388A>G, SLCO1B1 521T>C, CYP3A4 1B, CYP3A4 1G, and CYP3A5*3 Exhibits a Significant Alteration in the Pharmacokinetics of Atorvastatin Calcium

When the same treatment has different response: The role of pharmacogenomics in statin therapy

Contact Info

Product

Resources

About