Pharmacokinetic interactions between tacrolimus and Wuzhi capsule in liver transplant recipients: Genetic polymorphisms affect the drug interaction

Huang, Siqi; Song, Wei; Jiang, Shuangmiao; Li, Yuanchen; Wang, Min; Yang, Na; Zhu, Huaijun

doi:10.1016/j.cbi.2024.110906

Chemico-Biological Interactions

2024

DOI: 10.1016/j.cbi.2024.110906

|View full text |Cite

Pharmacokinetic interactions between tacrolimus and Wuzhi capsule in liver transplant recipients: Genetic polymorphisms affect the drug interaction

Siqi Huang,

Wei Song,

Shuangmiao Jiang

et al.

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Citation Types

Supporting

Mentioning

Contrasting

Year Published

2024

Publication Types

Select...

Article3

Relationship

Self Cite0

Independent3

Authors

Journals

Cited by 3 publications

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

Weight, CYP3A5 Genotype, and Voriconazole Co-administration Influence Tacrolimus Initial Dosage in Pediatric Lung Transplantation Recipients with Low Hematocrit based on a Simulation Model

Hu,

Pan,

et al. 2024

CPD

View full text Add to dashboard Cite

Objective: The method of administering the initial doses of tacrolimus in recipients of pediatric lung transplantation, especially in patients with low hematocrit, is not clear. The present study aims to explore whether weight, CYP3A5 genotype, and voriconazole co-administration influence tacrolimus initial dosage in recipients of pediatric lung transplantation with low hematocrit based on safety and efficacy using a simulation model. Methods: The present study utilized the tacrolimus population pharmacokinetic model, which was employed in lung transplantation recipients with low hematocrit. Results: For pediatric lung transplantation recipients not carrying CYP3A5*1 and without voriconazole, the recommended tacrolimus doses for weights of 10-13, 13-19, 19-22, 22-35, 35-38, and 38-40 kg are 0.03, 0.04, 0.05, 0.06, 0.07, and 0.08 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients carrying CYP3A5*1 and without voriconazole, the recommended tacrolimus doses for weights of 10-18, 18-30, and 30-40 kg are 0.06, 0.08, 0.11 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients not carrying CYP3A5*1 and with voriconazole, the recommended tacrolimus doses for weights of 10-20 and 20-40 kg are 0.02 and 0.03 mg/kg/day, which are split into two doses, respectively. For pediatric lung transplantation recipients carrying CYP3A5*1 and with voriconazole, the recommended tacrolimus doses for weights of 10-20, 20-33, and 33-40 kg are 0.03, 0.04, and 0.05 mg/kg/day, which are split into two doses, respectively. Conclusion: The present study is the first to recommend the initial dosages of tacrolimus in recipients of pediatric lung transplantation with low hematocrit using a simulation model.

show abstract

Weight, CYP3A5 Genotype, and Voriconazole Co-administration Influence Tacrolimus Initial Dosage in Pediatric Lung Transplantation Recipients with Low Hematocrit based on a Simulation Model

Hu,

Pan,

et al. 2024

CPD

View full text Add to dashboard Cite

show abstract

Effect of donor GSTM3 rs7483 genetic variant on tacrolimus elimination in the early period after liver transplantation

Zhang,

Chen,

Liu

et al. 2024

PeerJ

View full text Add to dashboard Cite

Purpose Glutathione S-transferase mu (GSTM) belongs to the group of phase II drug-metabolizing enzymes, and the GSTM1 genetic variant has been reported to have a potential association with the metabolism of immunosuppressive drug after renal transplantation. The effect of donor and recipient GSTMs genetic variants on tacrolimus (Tac) metabolism was the focus of our investigation in this study. Methods A total of 203 liver transplant patients were recruited for the study. In the training set (n = 110), twenty-one SNPs in five genes (GSTM1-5) were genotyped by the drug-metabolizing enzymes and transporter (DMET) microarray. CYP3A5 rs776746 and GSTM3 rs7483 were genotyped using a Mass ARRAY platform in the validating set (n = 93). Results Tac C/D ratios of donor GSTM3 rs7483 AA carriers were significantly lower than those with the G allele at weeks 1, 2, 3 and 4 after liver transplantation (LT). Multivariate analysis was conducted on the training set and validating set, donor and recipient CYP3A5 rs776746, donor GSTM3 rs7483 and total bilirubin were identified as independent predictors of Tac C/D ratios in the early period after LT. Combining CYP3A5 rs776746 and donor GSTM3 rs7483 genotypes, Tac C/D ratios were observed to be increasingly lower with increasing numbers of alleles associated with fast metabolism. Moreover, the risk of a supratherapeutic C0 (Tac > 15 ug/L) was significantly higher for poor metabolizers than the other groups at week 1 after LT. Conclusions There was a significant association between the donor GSTM3 rs7483 genetic variant and Tac metabolism in the early period after LT. Genotype classification might have a better predictive ability of the initial Tac doses.

show abstract

CYP3A4 and CYP3A5: the crucial roles in clinical drug metabolism and the significant implications of genetic polymorphisms

Zhang,

Wang,

Wang

et al. 2024

PeerJ

View full text Add to dashboard Cite

CYP3A, a key member of the cytochrome P450 (CYP450) superfamily, is integral to drug metabolism, processing a substantial portion of medications. Their role in drug metabolism is particularly prominent, as CYP3A4 and CYP3A5 metabolize approximately 30–50% of known drugs. The genetic polymorphism of CYP3A4/5 is significant inter-individual variability in enzymatic activity, which can result in different pharmacokinetic profiles in response to the same drug among individuals. These polymorphisms can lead to either increased drug toxicity or reduced therapeutic effects, requiring dosage adjustments based on genetic profiles. Consequently, the study of the enzymatic activity of CYP3A4/5 gene variants is of great importance for the formulation of personalized treatment regimens. This article first reviews the role of CYP3A4/5 in drug metabolism in the human body, including inhibitors and inducers of CYP3A4/5 and drug-drug interactions. In terms of genetic polymorphism, it discusses the detection methods, enzymatic kinetic characteristics, and clinical guidelines for CYP3A5. Finally, the article summarizes the importance of CYP3A4/5 in clinical applications, including personalized therapy, management of drug-drug interactions, and adjustment of drug doses. This review contributes to the understanding of the functions and genetic characteristics of CYP3A4/5, allowing for more effective clinical outcomes through optimized drug therapy.

show abstract

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

customersupport@researchsolutions.com

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Made with 💙 for researchers

Part of the Research Solutions Family.

Pharmacokinetic interactions between tacrolimus and Wuzhi capsule in liver transplant recipients: Genetic polymorphisms affect the drug interaction

Cited by 3 publications

References 35 publications

Weight, CYP3A5 Genotype, and Voriconazole Co-administration Influence Tacrolimus Initial Dosage in Pediatric Lung Transplantation Recipients with Low Hematocrit based on a Simulation Model

Weight, CYP3A5 Genotype, and Voriconazole Co-administration Influence Tacrolimus Initial Dosage in Pediatric Lung Transplantation Recipients with Low Hematocrit based on a Simulation Model

Effect of donor GSTM3 rs7483 genetic variant on tacrolimus elimination in the early period after liver transplantation

CYP3A4 and CYP3A5: the crucial roles in clinical drug metabolism and the significant implications of genetic polymorphisms

Contact Info

Product

Resources

About