Pharmacometrics: a quantitative tool of pharmacological research

Zheng, Qingshan; Li, Lujin

doi:10.1038/aps.2012.149

Cited by 12 publications

(11 citation statements)

References 16 publications

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“…However, due to the considerable pharmacokinetic variation among individuals ( 74 , 75 ), the optimal initial dose regimen of tacrolimus in pediatric and adolescent patients with LN has remained to be determined. Population pharmacokinetic models may be useful in predicting individualized therapy by integrating different effects of variables on drug exposure ( 76 ), which may determine the initial dosage in different diseases. This includes dose simulation of oxcarbazepine in pediatric patients with epilepsy ( 77 ), dose optimization of vancomycin in neonates and young infants ( 78 ), dose optimization of azithromycin in pediatric patients with community-acquired pneumonia ( 79 ), dose optimization of cyclosporin in pediatric patients with hemophagocytic lymphohistiocytosis ( 80 ) and dose optimization of tacrolimus in patients with nephritic syndrome ( 81 , 82 ).…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real‑world data

Chen

Wang

et al. 2020

Exp Ther Med

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The present study aimed to establish a population pharmacokinetics model of tacrolimus and further optimize the initial dosing regimen of tacrolimus in pediatric and adolescent patients with lupus nephritis (LN). Pediatric and adolescent patients with LN were recruited between August 2014 and September 2019 at the Children's Hospital of Fudan University (Shanghai, China). Relevant information was used to set up a population pharmacokinetics model with a Nonlinear Mixed Effect Model and the initial dosage regimen was simulated with the Monte Carlo method. Body weight and co-administration of wuzhi capsule were indicated to influence tacrolimus clearance in pediatric and adolescent patients with LN, and at the same body weight, the rate of tacrolimus clearance in patients without vs. with co-administration of wuzhi capsule was 1:0.71. In addition, in patients who were not administered wuzhi capsule, an initial dosage regimen of 0.15 mg/kg/day was recommended for a body weight of 10-23 kg and 0.10 mg/kg/day for 23-60 kg; in patients who were administered wuzhi capsule, an initial dosage regimen of 0.10 mg/kg/day was recommended for a body weight of 10-23 kg and 0.05 mg/kg/day for 23-60 kg. To the best of our knowledge, the present study was the first to establish a population pharmacokinetics model of tacrolimus in order to determine the optimal initial dosage regimen of tacrolimus in pediatric and adolescent patients with LN.

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Section: Discussionmentioning

confidence: 99%

Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real‑world data

Chen

Wang

et al. 2020

Exp Ther Med

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“…However, due to the narrow window of tacrolimus treatment, pharmacokinetics in vivo that are affected by child development and drug metabolism enzymes, it is difficult to determine the initial dosage of tacrolimus for children with systemic lupus erythematosus. Population pharmacokinetics has great potential to realize individualized therapy via integrating different effects of variables on drug exposure, which are then used for determining tacrolimus dose for different diseases. For example, the study by Hao et al evaluated the population pharmacokinetics of tacrolimus in paediatric nephrotic syndrome to optimize the dosing regimen.…”

Section: Discussionmentioning

confidence: 99%

Initial dose optimization of tacrolimus for children with systemic lupus erythematosus based on theCYP3A5polymorphism and coadministration with Wuzhi capsule

Chen

Wang

et al. 2019

J Clin Pharm Ther

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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.

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“…Cytotoxicity of compounds was assessed by a standard 3-(4,5-dimethylthiazolyl)-2,5diphenyltetrazolium bromide (MTT) assay as previously described [19]. Cells were plated on 96-well plates at a density of 110 cells per well 24 h prior to the addition of the MTT reagent.…”

Section: Cytotoxicitymentioning

confidence: 99%

Synthesis of Novel Amide Derivatives with In Vitro Antiproliferative and Cytotoxic Activity

Liu

Zhang

Yang

et al. 2012

Heteroatom Chemistry

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Some amide derivatives are highly valuable products with antiproliferative and cytotoxic bioactivity. In this paper, 12 novel amide compounds were synthesized correspondingly by boc‐protection glycine, deprotection, and condensation reactions. The antiproliferative and cytotoxic activity of these compounds was also evaluated by human cervical cancer (Hela) and hepatoma carcinoma (SK‐Hep‐1) cancer cell lines. The assay revealed that eight compounds (5a–d, 6a–d) exhibited activity against Hela cancer cells. Four of them (5a–d) also showed activity against SK‐Hep‐1 cancer cells. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 24:9–17, 2013; View this article online at http://wileyonlinelibrary.com. DOI 10.1002/hc.21057

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Pharmacometrics: a quantitative tool of pharmacological research

Cited by 12 publications

References 16 publications

Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real‑world data

Population pharmacokinetics model and initial dose optimization of tacrolimus in children and adolescents with lupus nephritis based on real‑world data

Initial dose optimization of tacrolimus for children with systemic lupus erythematosus based on theCYP3A5polymorphism and coadministration with Wuzhi capsule

Synthesis of Novel Amide Derivatives with In Vitro Antiproliferative and Cytotoxic Activity

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