7 results on '"You, Xiang"'
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2. Ceftaroline Dosage Optimized for Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling.
- Author
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Zhou, Jie, You, Xiang, Guo, Guimu, Ke, Meng, Xu, Jianwen, Ye, Lingling, Wu, Wanhong, Huang, Pinfang, and Lin, Cuihong
- Subjects
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BIOLOGICAL models , *BIOAVAILABILITY , *AGE distribution , *PEDIATRICS , *ANTI-infective agents , *KIDNEY diseases , *CEPHALOSPORINS , *DRUG monitoring , *PHARMACODYNAMICS , *CHILDREN - Abstract
Ceftaroline fosamil is a fifth‐generation cephalosporin approved as a treatment for adults and children with community‐acquired bacterial pneumonia and acute bacterial skin and skin structure infections. However, its pharmacokinetics have not been fully evaluated in children with renal impairment. This study aimed to propose proper ceftaroline dosages optimized for the renally impaired pediatric population using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of ceftaroline was established and verified to simulate its disposition in the healthy population and renally impaired adults and to predict the exposure in renally impaired pediatric patients. Consistency was confirmed between simulated and observed data after intravenous administration of various ceftaroline regimens; fold errors were within the 2‐fold error range. Among 6‐year‐old children, healthy subjects had 1.5‐fold, 2‐fold, and 2.6‐fold lower areas under the plasma concentration–time curve (AUCs) than the moderate, severe, and end‐stage renally impaired patient groups, respectively; among 1‐year‐old children, healthy subjects had 1.5‐fold, 2.1‐fold, and 2.5‐fold lower AUCs than the respective renally impaired patient groups; among 1‐month‐old children, healthy subjects had 1.5‐fold, 1.8‐fold, and 2.2‐fold lower AUCs than the respective renally impaired patient groups. The proposed dosage should be adjusted to 8, 6, and 5 mg/kg every 8 hours for patients aged ≥2 years to <18 years (≤33 kg) with moderate, severe, and end‐stage renal impairment, respectively; 5, 4, and 3 mg/kg every 8 hours for patients aged 2 months to <2 years with moderate, severe, and end‐stage renal impairment, respectively; 4, 3.5, and 2.5 mg/kg every 8 hours for patients 0 to <2 months of age with moderate, severe, and end‐stage renal impairment, respectively. Furthermore, pharmacodynamic investigations demonstrated that adequate antimicrobial effects were attained at the proposed doses in 3 age groups. Hence, our PBPK model can be an effective tool to support ceftaroline dosage proposals for renally impaired pediatric patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
3. Dosage Adjustment for Ceftazidime in Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling.
- Author
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Zhou, Jie, You, Xiang, Ke, Meng, Ye, Lingling, Wu, Wanhong, Huang, Pinfang, and Lin, Cuihong
- Subjects
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CHILD patients , *CEFTAZIDIME , *PHARMACOKINETICS , *CHRONIC kidney failure - Abstract
Physiologically based pharmacokinetic (PBPK) modeling has unique advantages in investigating the pharmacokinetics of drugs in special populations. Our aim is to design optimized dosing regimens for ceftazidime in renally-impaired pediatric patients using PBPK modeling. Models for healthy and renally-impaired adults were developed, verified, and adapted for children to predict ceftazidime exposure in pediatric patients with varying degrees of renal impairment, capturing age- and weight-related pharmacokinetic changes. We derived a dosage-adjusted regimen for renally-impaired children based on pharmacokinetic data and evaluated the pharmacodynamics of ceftazidime. The PBPK models adequately predicted ceftazidime exposures in populations after single- and multi-dose administrations, with fold error values within 1.1 between simulated and observed data. In moderate, severe, and end-stage renally-impaired pediatric patients, the areas under the plasma concentration-time curves (AUCs) were 1.87-fold, 3.56-fold, and 6.19-fold higher, respectively, than in healthy children when treated with the same dose of 50 mg/kg. Pharmacodynamic verification indicated that the recommended doses of 28, 15, and 8 mg/kg administered three times daily (every 8 h) to pediatric patients with moderate, severe, and end-stage renal disease, respectively, were sufficient to attain the target of maintaining the free plasma concentration at or above minimum inhibitory concentration (MIC) during 70% of the dosing interval (70% fT > MIC: nearly 100% target attainment for susceptible MIC of 4 mg/L and >70% for intermediate MIC of 8 mg/L). Our PBPK model can be an effective tool to support dosing recommendations in pediatric patients with different degrees of renal impairment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
4. Development of a Physiologically Based Pharmacokinetic Model for Prediction of Pramipexole Pharmacokinetics in Parkinson's Disease Patients With Renal Impairment.
- Author
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You, Xiang, Wu, Wanhong, Xu, Jing, Jiao, Zheng, Ke, Meng, Huang, Pinfang, and Lin, Cuihong
- Subjects
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CARRIER proteins , *DOSE-effect relationship in pharmacology , *GLOMERULAR filtration rate , *ION exchange resins , *KIDNEY diseases , *ORAL drug administration , *PARKINSON'S disease , *PHARMACEUTICAL arithmetic , *PRAMIPEXOLE , *INDIVIDUALIZED medicine , *STATISTICAL models - Abstract
Pramipexole is the first‐line medication recommended by the British National Institute for Health and Care Excellence. Pramipexole is predominantly eliminated by renal excretion. The aim was to develop a physiologically based pharmacokinetic (PBPK) model of pramipexole, providing a basis for its individualized administration. The role of glomerular filtration and organic cation transporter 2 (OCT2) in renal tubular secretion was considered. Plasma concentration‐time profiles of pramipexole were predicted and validated, first in healthy populations and then in PD patients with varied renal function. Finally, the pharmacokinetics of PD patients with different degrees of renal impairment were predicted. The simulated pharmacokinetic parameters, including maximum plasma concentration (Cmax), area under the plasma concentration‐time curve (AUC), time to maximum plasma concentration (tmax), and steady‐state trough plasma concentration values, obtained using the PBPK model were validated using fold error values, which were all smaller than 2. The successfully validated model supported that OCT2‐mediated tubular secretion was affected proportionally to changes in glomerular filtration for various degrees of renal impairment. The predicted AUC0‐inf values were increased 1.16‐, 1.76‐, 3.26‐, and 9.48‐fold in mild, moderate, and severe renal impairment and end‐stage renal disease (ESRD) subjects, resepctively, compared with PD patients with normal renal function. It appears that PD patients with mild renal impairment are unlikely to require dose adjustment (0.125 mg 3 times a day). The pramipexole dose should be reduced to approximately 0.125 mg twice daily, 0.125 mg once daily, and 0.0375 mg once daily in PD patients with moderate renal impairment, severe renal impairment, and ESRD, respectively. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
5. Prediction of Ticagrelor and its Active Metabolite in Liver Cirrhosis Populations Using a Physiologically Based Pharmacokinetic Model Involving Pharmacodynamics.
- Author
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Zhang, Min, You, Xiang, Ke, Meng, Jiao, Zheng, Wu, Hongwei, Huang, Pinfang, and Lin, Cuihong
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CIRRHOSIS of the liver , *PHARMACODYNAMICS , *ACUTE coronary syndrome , *PHARMACOKINETICS , *BLOOD platelet aggregation - Abstract
Ticagrelor, a P2Y 12 receptor antagonist, has been highly recommended for use in acute coronary syndrome. The major active metabolite (AM) is similar to the parent drug, which exhibits antiplatelet activity. The inhibition of platelet aggregation (IPA) is used as an assay to demonstrate the anticoagulant efficacy of ticagrelor. In this study, we developed a physiologically based pharmacokinetic (PBPK) model to predict the pharmacokinetics of ticagrelor and its AM and combined this model with a pharmacodynamics model to reflect potential pharmacodynamic alterations in liver cirrhosis populations. The simulated results obtained using the PBPK model were validated by fold error values, which were all smaller than 2. Comparisons of exposure in different classifications of liver cirrhosis indicated that exposure to ticagrelor increased significantly with an increase in the degree of cirrhosis severity, whereas exposure to AM was decreased. The total concentration of ticagrelor and AM was related to the IPA included in the Sigmoid E max model. The PBPK model of ticagrelor and AM could predict the pharmacokinetics of all populations, and a combination of PD models was used to extrapolate for predicting unknown scenarios. Liver cirrhosis may result in prolonged IPA, depending on the severity degree of this disease. The combined PBPK model including IPA can reveal changes in pharmacokinetics and pharmacodynamics in populations affected by liver cirrhosis and indicate the risk potential. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
6. A Physiologically Based Pharmacokinetic Model of Ertapenem in Pediatric Patients With Renal Impairment.
- Author
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Ye, Lingling, Ke, Meng, You, Xiang, Huang, Pinfang, and Lin, Cuihong
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PHARMACOKINETICS , *CHRONIC kidney failure , *DISABILITIES , *CHILD patients , *INTRAVENOUS therapy , *ERTAPENEM - Abstract
Ertapenem is a widely used antibiotic; however, its pharmacokinetics has not been fully evaluated in children with renal impairment. A physiologically based pharmacokinetic (PBPK) model of ertapenem was established and validated to simulate its disposition in the healthy population and adults with renal impairment, as well as to predict the exposure in pediatric patients with renal impairment. The simulated PBPK modeling results and the observed data of ertapenem after intravenous administration of various regimens were consistent according to the fold error values of less than 2. Furthermore, %T > MIC of ertapenem was evaluated using the PBPK model. The C max was not significantly changed in pediatric patients with renal impairment compared to healthy children. However, the AUC was 1.42-fold, 1.84-fold, 2.37-fold, and 3.52-fold higher in mild, moderate, severe renal impairment, and end-stage renal disease, respectively, than that in healthy children and the doses of ertapenem were reduced to 13 mg/kg b.i.d, 9 mg/kg b.i.d, 6 mg/kg b.i.d, and 5 mg/kg b.i.d, respectively. The probability of achieving 40%T > MIC (MIC ≤ 4 μg/mL) was nearly 100% throughout the recommended dosing interval. In conclusion, our model can be used as a tool to generate better predictions for the most effective ertapenem dosing in pediatric patients. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
7. Physiologically Based Pharmacokinetic Modeling and Dose Adjustment of Teicoplanin in Pediatric Patients With Renal Impairment.
- Author
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Xu, Jianwen, Lin, Rongfang, Chen, Yong, You, Xiang, Huang, Pinfang, and Lin, Cuihong
- Subjects
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PEDIATRICS , *INDIVIDUALIZED medicine , *KIDNEY diseases , *PHARMACEUTICAL arithmetic , *PEPTIDE antibiotics , *DESCRIPTIVE statistics - Abstract
The pharmacokinetics of teicoplanin differs in children as compared with adults, and especially in renally impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment‐related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with a <1.36‐fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration–time curve was predicted to increase 1.25‐fold, 1.95‐fold, and 2.82‐fold in pediatric patients with mild, moderate, and severe renal impairment, respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12‐hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild, moderate, and severe renal impairment, respectively, at a susceptible minimum inhibitory concentration <2 mg/L. In conclusion, our PBPK model with an incorporated Monte Carlo simulation can provide improved guidance on dosing in pediatric patients with differing renal function and provide a basis for precision therapy with teicoplanin. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
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