Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions

Gao, Ling; Xu, Hua; Qi, Ye; Li, Sichan; Wang, Jun; Mei, Yan; Niu, Changhe; Kang, Ting; Chen, Chen; Wang, Yan

doi:10.3389/fphar.2020.00552

Cited by 14 publications

(18 citation statements)

References 37 publications

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“…Gao et al reported dosing regimens for Chinese pediatrics to achieve the C min of > 10 mg/L. Three loading doses of 6–12 mg/kg every 12 h, followed by a maintenance doses of 8–10 mg/kg/day were required, which is similar to three loading doses of 10 mg/kg every 12 h, followed by a maintenance dose of 6–14 mg/kg/day in our study ( Gao et al, 2020 ). 2) Although antibiotic dosing as determined by PK/PD data was suggested, lack of practitioner familiarity, unclear benefit, time allocation and training requirements are the biggest obstacles to make it in clinical practice ( Kufel et al, 2019 ).…”

Section: Discussionsupporting

confidence: 64%

“…Moreover, it has been demonstrated that nearly 60% of children in pediatric intensive care unit (PICU) exhibit augmented renal clearance (ARC), resulting in low drug exposure due to enhanced excretion ( Van Der Heggen et al, 2019 ). Little is known about the PK of teicoplanin in children (eight studies in total), which greatly hinder the dosing optimization of teicoplanin in children, and only one of them involves Asian children ( Supplementary Table S1 ) ( Terragna et al, 1988 ; Reed et al, 1997 ; Aarons et al, 1998 ; Sanchez et al, 1999 ; Lukas et al, 2004 ; Ramos-Martin et al, 2014 ; Zhao et al, 2015 ; Gao et al, 2020 ). The objectives of this analysis were to: 1) determine the PK of teicoplanin in Asian children by using a population approach; 2) evaluate the standard dosage regimens of teicoplanin; and 3) establish a simulation-based dosage regimens in this vulnerable population.…”

Section: Introductionmentioning

confidence: 99%

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Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients

et al. 2020

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Objectives: The pharmacokinetics (PK) of teicoplanin differs in children compared with adults. Our aim was to determine the PK of teicoplanin in an Asian pediatric population and to optimize dosage regimens.Methods: This was a retrospective PK study and all the data were collected from hospitalized children. We developed a population PK model using sparse data, and Monte Carlo simulation was used to assess the ability of standard teicoplanin regimen and other different dosage regimens. The optimal dosing regimens were defined as achieving the target trough concentration (Cmin) of 10 mg/L and pharmacokinetic/pharmacodynamic (PK/PD, [AUC24/MIC]) of 125 for moderate infection. For severe infection, the optimal dosing regimens were defined as achieving the target 15 mg/L and AUC24/MIC of 345.Results: 159 children were included and 1.5 samples/children on average were provided. Estimated clearance of teicoplanin was 0.694 L/h (0.784/L/h/70 kg) and volume of distribution was 1.39 L. Teicoplanin standard loading dose was adequate for moderate infection, while 13 mg/kg was needed for severer infection. With standard maintenance doses, both patients with moderate and severe infection failed to achieve the target Cmin. 12 and 16 mg/kg/day were required to achieve a Cmin ≥ 10 and 15 mg/L, respectively. However, standard maintenance dose was adequate to achieve AUC24/MIC ≥ 125 for moderate infection, and 12 mg/kg/day was needed to achieve AUC24/MIC ≥ 345 for severe infection. Lower weight and serum creatinine were associated with higher dose.Conclusion: Optimal doses based on the target Cmin were higher than that based on the PK/PD target. To achieve the Cmin and PK/PD targets simultaneously, a standard loading dose was adequate for moderate infection based on simulation, while dosing higher than standard doses were required in other situation. Further clinical studies with rich sampling from children is required to confirm our findings.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients

et al. 2020

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“…Review of titles and abstracts led to the retrieval of 215 potentially relevant full‐text citations. After full‐text review, 25 citations met the criteria for inclusion 16–41 . The most common reason for exclusion was non‐pediatric population studies (190 citations), followed by lack of ARC data (24 citations).…”

Section: Resultsmentioning

confidence: 99%

Scoping review of augmented renal clearance in critically ill pediatric patients

2021

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Augmented renal clearance (ARC), a phenomenon of enhanced elimination of renal solutes, has been described in adult critically ill patients, but little is known about the phenomenon in children. The aim of this scoping review was to gather and summarize all evidence on ARC in pediatric patients to examine its breadth and depth including prevalence, risk factors, and pharmacokinetic alterations and identify any gaps for further areas of inquiry. PubMed, Embase, and Web of Science were searched for titles, abstracts, or keywords that focused on ARC. Non‐English studies, reviews, and nonhuman studies were excluded. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses for Scoping Reviews (PRISMA‐ScR) guidelines. Data were extracted on article type, study details, patient population, ARC definition and prevalence, methods of renal function assessment, and study results. A total of 215 citations were found with 25 citations meeting the criteria for inclusion in pediatrics (2102 total patients); the majority of studies (84%) focused on pharmacokinetics (PK) of antimicrobial agents. The median/mean age range was 1.25–12 years. There were a total of 10 different definitions of ARC. The prevalence of ARC ranged from 7.8% to 78%. The most common method for documenting creatinine clearance (CrCl) was the modified Schwartz equation (64%). Only 20% of studies reported risk factors for ARC including low serum creatinine, increasing age, febrile neutropenia, male, septic shock, and treatment with antibiotics. Glycopeptide antimicrobials were the most evaluated class (42.9%) among the 21 antimicrobial drug studies. All studies reported increased drug clearance and/or poor probability of achieving target concentrations of the agents studied. ARC showed variable prevalence in pediatric patients likely due to the lack of a standard definition and many studies not considering age‐related changes in CrCl with pediatric intensive care unit (PICU) patients. ARC was shown to impact PK of antibiotics commonly administered to pediatric patients, which may necessitate changes in standard dosing regimens.

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“… 17 Since teicoplanin is mainly excreted by the kidneys, 27 impaired renal function usually causes a decrease of teicoplanin clearance. 28 In addition, drug clearance and volume of distribution in children also changed with the increase of age and weight, further affecting the drug exposure. Strenger et al found that compared with school-age children, young children had significantly lower initial teicoplanin C min .…”

Section: Discussionmentioning

confidence: 99%

<p>Therapeutic Drug Monitoring and Nephrotoxicity of Teicoplanin Therapy in Chinese Children: A Retrospective Study</p>

Sun

Zhang

et al. 2020

IDR

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Purpose This study aims to 1) describe the distribution characteristics of teicoplanin trough concentration ( C min ) and explore the related influencing factors and 2) evaluate the nephrotoxicity of teicoplanin in children. Patients and Methods A cohort of children who were treated with teicoplanin intravenously were included in this retrospective study. Regression analysis was performed to explore the factors associated with the fluctuations of teicoplanin C min and the development of nephrotoxicity. Classification and regression tree analysis was used to identify the population at high risk for teicoplanin nephrotoxicity. Results A total of 269 plasma samples from 186 children were collected. Underexposure ( C min < 10 mg/L) was documented in 52.7% of cases. The C min /dose after administering the loading dose was strongly associated with age ( P = 0.008), weight ( P = 0.039), and serum creatinine ( P = 0.022). The C min /dose after administering the maintenance dose was strongly associated with gender ( P = 0.014) and serum creatinine ( P = 0.006). C min ( P = 0.012) and the concomitant treatment with amphotericin B ( P = 0.001) were the independent risk factors for teicoplanin-related nephrotoxicity. Children who were concomitantly treated by amphotericin B with teicoplanin C min > 9.81 mg/L or patients with teicoplanin C min > 21.94 mg/L were at high risk for nephrotoxicity. Conclusion The fluctuations of teicoplanin C min could be affected by age, weight, gender, and serum creatinine. C min and concomitant treatment with amphotericin B were the independent risk factors for nephrotoxicity. We suggested that the therapeutic drug monitoring of teicoplanin should be performed in children.

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Population Pharmacokinetics and Dosage Optimization of Teicoplanin in Children With Different Renal Functions

Cited by 14 publications

References 37 publications

Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients

Population Pharmacokinetics and Model-Based Dosing Optimization of Teicoplanin in Pediatric Patients

Scoping review of augmented renal clearance in critically ill pediatric patients

<p>Therapeutic Drug Monitoring and Nephrotoxicity of Teicoplanin Therapy in Chinese Children: A Retrospective Study</p>

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