Initial dose optimization of tacrolimus for children with systemic lupus erythematosus based on the CYP3A5 polymorphism and coadministration with Wuzhi capsule.
What is known and objectives: Tacrolimus, an immunosuppressant, has been used to treat paediatric systemic lupus erythematosus, but the optimal initial regimen is not clear. The purpose of this study was to explore the optimal initial dose of tacrolimus for children with systemic lupus erythematosus...
| Published in: | Journal of Clinical Pharmacy & Therapeutics Vol. 45; no. 2; pp. 309 - 318 |
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| Main Authors: | , , , |
| Format: | equations & formulas research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
Apr2020
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| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=142038952&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 142038952 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 02694727 EV4 jtl: Journal of Clinical Pharmacy & Therapeutics issn: 02694727 maglogo: Y pubinfo: dt: Apr2020 vid: 45 iid: 2 pid: 480 pub: Wiley-Blackwell place: Malden, Massachusetts artinfo: ui: 142038952 142038952 145835419 142038952 10.1111/jcpt.13072 142038952 ppf: 309 ppct: 9 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: Initial dose optimization of tacrolimus for children with systemic lupus erythematosus based on the CYP3A5 polymorphism and coadministration with Wuzhi capsule. aug: au: Chen, Xiao Wang, Dongdong Xu, Hong Li, Zhiping affil: Department of Pharmacy, Children's Hospital of Fudan University, Shanghai, China sug: subj: Tacrolimus Administration and Dosage Tacrolimus Therapeutic Use Tacrolimus Pharmacokinetics Fruit Administration and Dosage Capsules Lupus Erythematosus, Systemic Drug Therapy Cytochrome P-450 Enzyme System Polymorphism, Genetic Pharmacogenetics Lupus Erythematosus, Systemic Familial and Genetic Pediatric Care Human Linear Regression Genotype Alleles Child Adolescence Child: 6-12 years Adolescent: 13-18 years ab: What is known and objectives: Tacrolimus, an immunosuppressant, has been used to treat paediatric systemic lupus erythematosus, but the optimal initial regimen is not clear. The purpose of this study was to explore the optimal initial dose of tacrolimus for children with systemic lupus erythematosus using population pharmacokinetics and pharmacogenomics. Methods: Clinical information, tacrolimus concentrations and related genetic polymorphisms were incorporated into a model using non‐linear mixed‐effects modelling (NONMEM) analysis. Results and discussion: The results showed that weight, the CYP3A5 genotype and combined treatment with Wuzhi capsule can affect tacrolimus clearance in children with systemic lupus erythematosus. Furthermore, at the same weight, the ratios of tacrolimus clearance were 1:2.49:0.57:1.4193 from people who were CYP3A5*3/*3 and did not take Wuzhi capsule, people who had the CYP3A5*1 allele and did not take Wuzhi capsule, people who were CYP3A5*3/*3 and took Wuzhi capsule, and people who had the CYP3A5*1 allele and took Wuzhi capsule, respectively. In addition, we found that 0.10 mg/kg split into two doses was suitable for people with weights from 10 to 60 kg who were CYP3A5*3/*3 and did not take Wuzhi capsule, who were CYP3A5*3/*3 and took Wuzhi capsule, and who had the CYP3A5*1 allele and took Wuzhi capsule. In people who had the CYP3A5*1 allele and did not take Wuzhi capsule, 0.15 mg/kg split into two doses was appropriate for those with weights from 10 to 40 kg and 0.10 mg/kg split into two doses was appropriate for those with weights from 40 to 60 kg. What is new and conclusion: This study is the first study to recommend an optimal initial regimen of tacrolimus for children with systemic lupus erythematosus based on the CYP3A5 polymorphism and coadministration of Wuzhi capsule. pubtype: Academic Journal doctype: equations & formulas research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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