Population Pharmacokinetic Models of Vancomycin in Paediatric Patients: A Systematic Review

Chung, Erin; Sen, Jonathan; Patel, Priya; Seto, Winnie

doi:10.1007/s40262-021-01027-9

Cited by 13 publications

(22 citation statements)

References 97 publications

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“…The methodological quality of each included analysis was assessed by the National Institutes of Health (NIH) study quality assessment tool for case series studies in this review. This tool was developed by methodologists and the NIH based on quality assessment methods and concepts and can be used for nonrandomized studies and case series, which are commonly applied in systematic reviews that include observational studies ( 25 ).…”

Section: Methodsmentioning

confidence: 99%

Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review

Shang

Huang

et al. 2022

Front. Immunol.

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Aims and backgroundA number of population pharmacokinetic (PPK) models of anti-programmed cell death-1 (PD-1) monoclonal antibodies (mAbs) in multiple tumor types have been published to characterize the influencing factors of their pharmacokinetics. This review described PPK models of anti-PD-1 mAbs that investigate the magnitude and types of covariate effects in PK parameters, provide a reference for building PPK models of other anti-PD-1 mAbs, and identify areas requiring additional research to facilitate the application of PPK models.MethodsA systematic search for analyses of PPK models of eleven anti-PD-1 mAbs on the market that were carried out in humans was conducted using PubMed, Embase, and the Cochrane Library. The search covered the period from the inception of the databases to April 2022.ResultsCurrently, there are fourteen analyses on PPK models of anti-PD-1 mAbs summarized in this review, including seven models that refer to nivolumab, four referring to pembrolizumab, one referring to cemiplimab, one referring to camrelizumab, and one referred to dostarlimab. Most analyses described the pharmacokinetics of anti-PD-1 mAbs with a two-compartment model with time-varying clearance (CL) and a sigmoidal maximum effect. The estimated CL and volume of distribution in the central (VC) ranged from 0.179 to 0.290 L/day and 2.98 to 4.46 L, respectively. The median (range) of interindividual variability (IIV) for CL and VC was 30.9% (8.7%–50.8%) and 29.0% (4.32%–40.7%), respectively. The commonly identified significant covariates were body weight (BW) on CL and VC, and albumin (ALB), tumor type, sex, and performance status (PS) on CL. Other less assessed significant covariates included lactate dehydrogenase (LDH), immunoglobulin G (IgG), ipilimumab coadministration (IPICO) on CL, and body mass index (BMI), malignant pleural mesothelioma (MESO) on VC.ConclusionThis review provides detailed information about the characteristics of PPK models of anti-PD-1 mAbs, the effects of covariates on PK parameters, and the current status of the application of the models. ALB, BW, specific tumor type, sex, and PS should be considered for the future development of the PPK model of anti-PD-1 mAbs. Other potential covariates that were assessed less frequently but still have significance (e.g., LDH, IgG, and IPICO) should not be ignored. Thus, further research and thorough investigation are needed to assess new or potential covariates, which will pave the way for personalized anti-PD-1 mAbs therapy.

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Section: Methodsmentioning

confidence: 99%

Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review

Shang

Huang

et al. 2022

Front. Immunol.

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“…1 Intravenous vancomycin is the drug of choice to treat CoNS sepsis, yet dosing in neonates remains a challenge due to significant pharmacokinetic variability from the influence of maturation and organ function. [2][3][4] Population pharmacokinetic (popPK) models can be used to personalize dosing and improve target attainment for vancomycin trough concentration or area under the concentration-time curve (AUC 24h ). A recent systematic review assessed multiple popPK models and highlighted the lack of comprehensive external evaluation to determine the accuracy and precision of the published models.…”

Section: Introductionmentioning

confidence: 99%

“…A recent systematic review assessed multiple popPK models and highlighted the lack of comprehensive external evaluation to determine the accuracy and precision of the published models. 4 Therefore, it remains unclear which popPK model should be used with the best predictive performance to develop initial vancomycin dosing guidelines leading to variations in dosing recommendations reported in the literature. 4 Historically, the recommended starting doses of vancomycin at The Hospital for Sick Children (SickKids®) were stratified by body weight (WT) or postmenstrual age (PMA) based on a study published in 1987.…”

Section: Introductionmentioning

confidence: 99%

“…4 Therefore, it remains unclear which popPK model should be used with the best predictive performance to develop initial vancomycin dosing guidelines leading to variations in dosing recommendations reported in the literature. 4 Historically, the recommended starting doses of vancomycin at The Hospital for Sick Children (SickKids®) were stratified by body weight (WT) or postmenstrual age (PMA) based on a study published in 1987. 5,6 This pharmacokinetic study had some limitations including a small sample size of 20 preterm infants and using a vancomycin target peak concentration of 30-40 mg/L and trough concentration of <10 mg/L, which differ from current practice.…”

Section: Introductionmentioning

confidence: 99%

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Using population pharmacokinetics to optimize initial vancomycin dosing guidelines for neonates to treat sepsis caused by coagulase‐negative staphylococcus

Chung

Seto

2023

Pharmacotherapy

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IntroductionVancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates.ObjectivesThe primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Secondly, the predictive performance of this popPK model was compared with published popPK models.MethodsThis is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modelling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase‐negative staphylococci (CoNS).ResultsAmong 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10‐15 mg/L) for central nervous system infections and 43% were outside target range (5‐12 mg/L) for other infections using the institution's vancomycin dosing. A one‐compartment model best described the observed data with a mean clearance of 0.11±0.03 L/kg/h and volume of distribution (V) of 1.02±0.08 L/kg. Body weight, postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance (p<0.001) and body weight was a significant covariate associated with V (p=0.009). Our study's popPK model has similar or better accuracy and precision than other published models. MCS‐derived vancomycin doses from the validated model achieved >90% target attainment for a steady state trough target range of 10‐15 mg/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis.ConclusionA vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.

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“…Vancomycin is one of the most widely used antibiotics for the treatment of serious infectious caused by Gram-positive bacteria.Since the 1960s, vancomycin has served as the drug of choice for treatment of neonatal infection especially caused by MRSA and CoNS [7]. In the neonatal population, there was wide inter-individual variability in pharmacokinetic parameters along with developmental variations in physiological and pathological factors affecting therapeutic effectiveness of medications as these neonates mature and grow [8].There were also large individual differences in vancomycin plasma concentration of neonates, therefore, safety and e cacy are not assured [9].The pharmacodynamic and pharmacokinetic pro les of vancomycin in neonatal population have been previously reported. However, a consensus still has not been reached about optimal recommended dose [10].Few studies on individualized dosage regimen of vancomycin are available relating particularly to distribution of pathogens and clinical outcome.Therefore, we sought to optimise the drug-dosing regimen based on Monte Carlo Simulation.…”

Section: Introductionmentioning

confidence: 99%

Vancomycin Dosing Regimens based on Monte Carlo Simulation for Treated Gram-positive cocci Infection in neonates: A retrospective observational study

Zhao

Liu

Chang

et al. 2022

Preprint

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Background: The pharmacodynamic and pharmacokinetic profiles of vancomycin in neonatal population have been previously reported. However, a consensus still has not been reached about optimal recommended dose. Few studies on neonatal population are available relating particularly to distribution of pathogens and clinical outcome.Therefore, we sought to optimise the drug-dosing regimen based on Monte Carlo Simulation and conducted a retrospective observational study to assess the trough concentration and clinical efficacy. Methods: We collected data from neonates who were treated with vancomycin from November 2018 to December 2021. Based on the inclusion criteria, pharmacokinetic model group and observation group were selected for further inclusion. The recommended pharmacokinetic-pharmacodynamic(PK-PD) target AUC/MIC ratio for vancomycin is ≥400. The achieved goal of the probability of target attainment (PTA) and a cumulative fraction of response (CFR) were ≥90%. Monte-Carlo simulations were performed to identify optimal dosing regimens. Statistical analysis were performed to compare trough concentrations and effectiveness of the different treatment options. Results: We collected pharmacokinetic data on a total of 137 neonates ( 92 male and 45 female) and 124 neonates ( 180 dosing regimens and 180 plasma trough concentration) were retrospectively analyzed in this study. The recommended doses required to achieve the goal of PTA or CFR from 25 to 225mg/d depending on PK-PD target in different subgroups. Recommended dosage regimen group ( n=80 ) presented higher values (P＜0.05）in trough concentration than in not-recommended groups ( n=100 ), yet the target concentration ( 5-15mg/l ) compliance rate indicates no significant differences (P＞0.05). Recommended dosage neonate group ( n=53 ) presented higher clinical response rate (P＜0.05）than in not-recommended groups ( n=71 ). Conclusion: Large differences of required daily dose exist among different newborn subgroups. A higher trough level and clinical efficacy was reached in simulated recommended doses regimen. However target concentration compliance rate indicates no significant change. A more scientific and standard study of multi-center were needed to optimize recommended dose and evaluate the real-world efficacy and safety of vancomycin.

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Population Pharmacokinetic Models of Vancomycin in Paediatric Patients: A Systematic Review

Cited by 13 publications

References 97 publications

Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review

Population pharmacokinetic models of anti-PD-1 mAbs in patients with multiple tumor types: A systematic review

Using population pharmacokinetics to optimize initial vancomycin dosing guidelines for neonates to treat sepsis caused by coagulase‐negative staphylococcus

Vancomycin Dosing Regimens based on Monte Carlo Simulation for Treated Gram-positive cocci Infection in neonates: A retrospective observational study

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