Evidence map›Paper›PMID 31932875›Full record

ArticleEuropean journal of clinical pharmacology2020

Variability of voriconazole concentrations in patients with hematopoietic stem cell transplantation and hematological malignancies: influence of loading dose, procalcitonin, and pregnane X receptor polymorphisms.

Guangting Zeng, Linlin Wang, Lihong Shi, Huilan Li, Miaomiao Zhu, Jia Luo, Zanling Zhang

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In one paragraph

Article in European journal of clinical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Guangting ZengDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Linlin WangDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Lihong ShiSichuan cancer hospital & institute, Chengdu, Sichuan, China.
Huilan LiDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Miaomiao ZhuTongji Medical College, Huazhong University of Science and Technology, Wuhan Mental Health Centre; Wuhan Hospital for Psychotherapy, Wuhan, Hubei, China.
Jia LuoDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zanling ZhangDepartment of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan, China. zanlingzhang2015@126.com.ORCID http://orcid.org/0000-0002-8707-0487
Central South University · CNHuazhong University of Science and Technology · CNSichuan Cancer Hospital · CN

Funding

Natural Science Foundation of Hunan Province No.2017JJ2398
6 · The paper itself

Abstract

aimsVoriconazole (VCZ) displays highly variable pharmacokinetics affecting treatment efficacy and safety. We aimed to identify the factors affecting VCZ steady-state trough concentration (Cssmin) to provide evidence for optimizing VCZ treatment regimens.

methodsA total of 510 Cssmin of 172 patients with hematopoietic stem cell transplantation and hematologic malignancies and their clinical characteristics and genotypes of FMO, POR, and PXR were included in this study.

resultsIn univariate analysis, the standard loading dose of VCZ significantly increased the Cssmin of VCZ (P < 0.001). The Cssmin of VCZ was significantly correlated with patients' total bilirubin (TB) (P < 0.001) and procalcitonin (PCT) (P < 0.001). FMO3 rs2266780 (P = 0.025), POR rs10954732 (P = 0.015), PXR rs2461817 (P = 0.010), PXR rs7643645 (P = 0.003), PXR rs3732359 (P = 0.014), PXR rs3814057 (P = 0.005), and PXR rs6785049 (P = 0.013) have a significant effect on Cssmin of VCZ. Loading dose, TB, PCT level, and PXRrs3814057 polymorphism were independent influencing factors of VCZ Cssmin in the analysis of multivariate linear regression. And loading dose, PCT, and PXR rs3814057 had significant effects on the probability of the therapeutic window of VCZ.

conclusionThe high variability of VCZ Cssmin may be partially explained by loading dose, liver function, inflammation, and PXR polymorphisms. This study suggests the VCZ standard loading dose regimen significantly increased Cssmin and probability of the therapeutic window providing treatment benefits. Patients in the high PCT group may be more likely to exceed 5.5 μg/mL, thus suffering from VCZ toxicity.

Indexed as

Hematologic NeoplasmsHematopoietic Stem Cell TransplantationPolymorphism, Single NucleotideAntifungal AgentsDrug MonitoringFemaleGenotypeHumansMaleMycosesPharmacogeneticsPregnane X ReceptorProcalcitoninRetrospective StudiesVoriconazoleAntifungal AgentsNR1I2 protein, humanPregnane X ReceptorProcalcitoninVoriconazoleFMO3Hematological malignanciesLoading dosePORProcalcitoninPXRVoriconazole

Identifiers

PMID31932875
OpenAlexW3000283565

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.