A novel random forest integrative approach based on endogenous CYP3A4 phenotype for predicting tacrolimus concentrations and dosages in Chinese renal transplant patients.
What is known and objective: Personalized treatment with tacrolimus has remained a challenge. The present study aimed to evaluate the potential of an integrative approach to predict individual tacrolimus concentrations and dosages based on endogenous CYP3A4 phenotype, CYP3A5 genotype and clinical va...
| Published in: | Journal of Clinical Pharmacy & Therapeutics Vol. 45; no. 2; pp. 318 - 324 |
|---|---|
| Main Authors: | , , , , , , |
| Format: | research tables/charts Journal Article |
| Published: |
Wiley-Blackwell
Apr2020
|
| Online Access: | View this record in EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=142038954&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 142038954 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: 142038954 142038954 145870015 142038954 10.1111/jcpt.13074 142038954 ppf: 318 ppct: 6 formats: fmt: – @attributes: type: T – @attributes: type: C – @attributes: type: P tig: atl: A novel random forest integrative approach based on endogenous CYP3A4 phenotype for predicting tacrolimus concentrations and dosages in Chinese renal transplant patients. aug: au: Cai, Ningfang Zhang, Xiujin Zheng, Chao Zhu, Lijun Zhu, Minfeng Cheng, Zeneng Luo, Xi affil: Department of Pharmacy, Xiamen Children's Hospital, Xiamen, China sug: subj: Cytochrome P-450 Enzyme System Urine Phenotype Evaluation Genotype Evaluation Biological Markers China Tacrolimus Pharmacokinetics Tacrolimus Administration and Dosage Kidney Transplantation China Transplant Recipients China Human Chinese Persons China Algorithms Urinalysis Hydrocortisone Urine Cortisone Urine ab: What is known and objective: Personalized treatment with tacrolimus has remained a challenge. The present study aimed to evaluate the potential of an integrative approach to predict individual tacrolimus concentrations and dosages based on endogenous CYP3A4 phenotype, CYP3A5 genotype and clinical variables. Methods: A random forest (RF) algorithm which incorporated an endogenous CYP3A4 phenotype (assessed by urinary ratio of 6β‐hydroxycortisol and 6β‐hydroxycortisone to cortisol and cortisone), CYP3A5*3 genotype and other clinical determinants of tacrolimus disposition was performed in 182 medically stable renal transplant recipients. Results and discussion: The results suggested that endogenous CYP3A4 phenotype was the most important determinant of tacrolimus concentrations and dose requirements. RF models provided high goodness of fit (R2) with.92 and.95 for the prediction of tacrolimus trough concentrations and dosages, respectively, as well as high predictability (Q2) with 0.63 and 0.70, respectively. Significant correlations existed between experimental and predictive data. What is new and conclusion: In summary, endogenous CYP3A4 phenotype is a critical biomarker for the determination of tacrolimus disposition. This predictive RF approach based on CYP3A4 biomarker with the combination of CYP3A5*3 genotype and other clinical variables can be used for predicting tacrolimus concentrations and dosages, which may serve as a useful tool in individualized tacrolimus dosing. pubtype: Academic Journal doctype: research tables/charts Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
|---|