Pharmacokinetics and Pharmacodynamics of Drugs in Obese Pediatric Patients: How to Map Uncharted Clinical Territories

Krekels, Elke H. J.; Knibbe, Catherijne A. J.

doi:10.1007/164_2019_250

Cited by 3 publications

(2 citation statements)

References 93 publications

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“…Clinical trials in obese children can be methodologically challenging since age-and obesity-related influences are both reflected in a child's body weight; i.e., body weight can increase as a result of growth and development (weight for age), and of overweight or obesity (excess weight) (8). Pharmacokinetic trials in pediatric obesity should ideally include an in-depth analysis that allows for the study of the distinct influence of maturation versus overweight on drug pharmacokinetics (9), as has been demonstrated for busulfan, midazolam, and metformin (10)(11)(12).…”

Section: Introductionmentioning

confidence: 99%

Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

Smit

Goulooze

Brüggemann³

et al. 2021

AAPS J

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Vancomycin is an effective but potentially nephrotoxic antibiotic commonly used for severe infections. Dosing guidelines for vancomycin in obese children and adolescents with or without renal impairment are currently lacking. This study describes the pharmacokinetics of vancomycin in a large pediatric cohort with varying degrees of obesity and renal function to design practical dosing guidelines for this population. A multi-center retrospective population pharmacokinetic study was conducted using data from patients aged 1−18 years who received >1 dose of vancomycin and had ≥1 vancomycin concentration measured between January 2006 and December 2012. Besides pharmacokinetic data, age, gender, body weight, creatinine clearance (CLcr, bedside Schwartz equation), ward, race, and neutropenic status were collected. Population pharmacokinetic analysis and simulations were performed using NONMEM7.4. A total of 1892 patients (5524 samples) were included, with total body weight (TBW) ranging 6−188 kg (1344 normal weight, 247 overweight, and 301 obese patients) and CLcr down to 8.6 mL/min/1.73 m2. The two-compartment model, with clearance (CL) significantly increasing with TBW and CLcr, central and peripheral volume of distribution and inter-compartmental clearance increasing with TBW, performed well for all age, weight, and renal function ranges. A dosing guideline is proposed that integrates body weight and CLcr resulting in effective and safe exposures across all ages, body weight, and renal functions in the pediatric population. We have characterized the full pharmacokinetic profile of vancomycin in obese children and adolescents aged 1−18 years and propose a practical dosing guideline that integrates both body weight and renal function.

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Section: Introductionmentioning

confidence: 99%

Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

Smit

Goulooze

Brüggemann³

et al. 2021

AAPS J

Self Cite

View full text Add to dashboard Cite

show abstract

“…It is known that the main physiologic changes influencing the absorption of drugs in the obese adult population comprise an increased gastric emptying time, intestinal permeability, splenic blood flow, and increased or decreased intestinal enzyme activity (Smit et al, 2018;Krekels & Knibbe, 2020). Amoxicillin is known to be absorbed by both passive and active transport processes but it is considered a BCS class 1/2, being eventually less influenced by these issues (Thambavita et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Amoxicillin dosing and pharmacokinetics in obesity for the treatment of bacterial respiratory infection secondary to COVID-19: a systematic review

Rosa

Silva²,

Yamada³

et al. 2022

RSD

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Objective: To conduct a systematic review of Amoxicillin (AMX) dosing and pharmacokinetics (PK) in obese subjects for the treatment of the outpatient respiratory tract infection which may be a secondary co-infection with COVID-19. Methodology: A systematic review was performed up to January 2022 on MEDLINE, EMBASE, and Web of Science. Full-text manuscripts describing AMX dosing for respiratory infection or PK in obese children, adults, and RYGB bariatric patients treated with AMX were included. Results: A total of 179 records were screened, of which 8 met the inclusion criteria. Four studies described AMX dosing in obese children and adults, while 4 described PK in obese adults and RYGB bariatric subjects. Overall, in the dosing studies, 54% of children >20 kg and 10% <40 kg with respiratory infection were considered underdosed, according to guidelines or recommendations. Underdosing of 10% occurred in both overweight and non-obese children’s groups. For morbidly obese adults, 70% were considered underdosed. In the PK studies, obese and bariatric adult subjects showed reduced exposure compared to normal weight patients for all AMX formulations. Conclusion: More PK studies are needed to confirm the optimal dose of AMX for obese patients, particularly in children. However, considering that all obese and bariatric adults had reduced exposure compared to subjects of normal weight, 1 g 8/8h should be recommended and liquid formulations are preferable for bariatric patients. To minimize the risks of therapeutic failure and avoid toxicity, a higher threshold of doses should be prescribed for obese children.

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The Use of Remote Learning Techniques for Pediatric Cardiopulmonary Resuscitation Simulation Highlighting the Intersection Between Pediatric Advanced Life Support (PALS) and Advanced Cardiac Life Support (ACLS) Pathways

Stokes,

Ismail,

Creamer

2024

Cureus

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Introduction: Medical simulation education has expanded in the remote learning sphere, providing educational opportunities to under-resourced areas and the ability to engage learners limited by time or geographic location. Pediatric resuscitation training has historically been in-person relying on Pediatric Advanced Life Support (PALS) algorithms, yet many pediatric providers are often faced with treating adult or adult-sized patients. Our goal was to develop a tele-simulation remote learning module highlighting possible diagnoses and scenarios that require adult treatment-minded approaches for the pediatric clinician, including the use of Advanced Cardiac Life Support (ACLS) algorithms. Methods: This simulation curriculum was offered in 2020 and 2022. The sessions were created for pediatric hospitalists and presented over an online video platform with visual aids to simulate being in a patient room. All three cases had the same base stem scenario and focused on a narcotic overdose, massive pulmonary embolism (PE), and torsades de pointes from polypharmacy-induced QTc prolongation. A multimodal assessment approach captured post-simulation comfort level with case content, information recall up to two years later, and pre- and post-test assessments of clinical knowledge improvement. Results:Eighty-one simulation slots were filled by 56 clinicians over two years. Fifty-one completed course evaluations averaged a score of 4.95 on a 5-point Likert scale survey. Increased comfort level was statistically significant across all learning objectives. The most significant improvements were in the domains of ACLS algorithm use and understanding when to terminate unsuccessful resuscitation efforts. Pre- and post-test results demonstrated statistically significant (p<0.001) evidence of knowledge transfer in ACLS and PALS content. Conclusion: Tele-simulation using an online video platform and well-defined visual aids is a useful option when in-person resuscitation simulation is not available. Practice and reinforcement of ACLS algorithms in pediatrics was found to be meaningful to clinicians who take care of patients of varying ages and sizes.

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Pharmacokinetics and Pharmacodynamics of Drugs in Obese Pediatric Patients: How to Map Uncharted Clinical Territories

Cited by 3 publications

References 93 publications

Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

Dosing Recommendations for Vancomycin in Children and Adolescents with Varying Levels of Obesity and Renal Dysfunction: a Population Pharmacokinetic Study in 1892 Children Aged 1–18 Years

Amoxicillin dosing and pharmacokinetics in obesity for the treatment of bacterial respiratory infection secondary to COVID-19: a systematic review

The Use of Remote Learning Techniques for Pediatric Cardiopulmonary Resuscitation Simulation Highlighting the Intersection Between Pediatric Advanced Life Support (PALS) and Advanced Cardiac Life Support (ACLS) Pathways

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