scholarly journals Medication Dosage in Overweight and Obese Children

2017 ◽  
Vol 22 (1) ◽  
pp. 81-83 ◽  
Author(s):  
Kelly L. Matson ◽  
Evan R. Horton ◽  
Amanda C. Capino ◽  
Keyword(s):  
Hepatic Clearance ◽  
Position Statement ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Overweight Children ◽  
Obese Children ◽  
Patients Âgés ◽  
Adult Dose ◽  
Total Body ◽  
State Concentration

Approximately 31.8% of U.S. children ages 2 to 19 years are considered overweight or obese. This creates significant challenges to dosing medications that are primarily weight based (mg/kg) and in predicting pharmacokinetics parameters in pediatric patients. Obese individuals generally have a larger volume of distribution for lipophilic medications. Conversely, the Vd of hydrophilic medications may be increased or decreased due to increased lean body mass, blood volume, and decrease percentage of total body water. They may also experience decreased hepatic clearance secondary to fatty infiltrates of the liver. Hence, obesity may affect loading dose, dosage interval, plasma half-life, and time to reach steady-state concentration for various medications. Weight-based dosing is also a cause for potential medication errors. This position statement of the Pediatric Pharmacy Advocacy Group recommends that weight-based dosing should be used in patients ages < 18 years who are < 40 kg; weight-based dosing should be used in patients ≥ 40 kg, unless, unless the recommended adult dose for the specific indication is exceeded; clinicians should use pharmacokinetic analysis for adjusting medications in overweight/obese children; and research efforts continue to evaluate dosing of medications in obese/overweight children.

Vancomycin volume of distribution estimation in adults with class III obesity

2019 ◽  
Author(s):  
Ryan D Dunn ◽  
Ryan L Crass ◽  
Joseph Hong ◽  
Manjunath P Pai ◽  
Lynne C Krop
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Patient Specific ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Parameter Estimates ◽  
Class Iii ◽  
Class Iii Obesity ◽  
Total Body

Abstract Purpose To compare methods of estimating vancomycin volume of distribution (V) in adults with class III obesity. Methods A retrospective, multicenter pharmacokinetic analysis of adults treated with vancomycin and monitored through measurement of peak and trough concentrations was performed. Individual pharmacokinetic parameter estimates were obtained via maximum a posteriori Bayesian analysis. The relationship between V and body weight was assessed using linear regression. Mean bias and root-mean-square error (RMSE) were calculated to assess the precision of multiple methods of estimating V. Results Of 241 patients included in the study sample, 159 (66.0%) had a BMI of 40.0–49.9 kg/m2, and 82 (34.0%) had a BMI of ≥50.0 kg/m2. The median (5th, 95th percentile) weight of patients was 136 (103, 204) kg, and baseline characteristics were similar between BMI groups. The mean ± S.D. V was lower in patients with a BMI of 40.0–49.9 kg/m2 than in those with a BMI of ≥50.0 kg/m2 (72.4 ± 19.6 L versus 79.3 ± 20.6 L, p = 0.009); however, body size poorly predicted V in regression analyses (R2 < 0.20). A fixed estimate of V (75 L) or use of 0.52 L/kg by total body weight yielded similar bias and error in this population. Conclusion Results of the largest analysis of vancomycin V in class III obesity to date indicated that use of a fixed V value (75 L) and use of a TBW-based estimate (0.52 L/kg) for estimation of vancomycin V in patients with a BMI of ≥40.0 kg/m2 have similar bias. Two postdistribution vancomycin concentrations are needed to accurately determine patient-specific pharmacokinetic parameters, estimate AUC, and improve the precision of vancomycin dosing in this patient population.

scholarly journals Can Bioimpedance Determine the Volume of Distribution of Antibiotics in Sepsis?

2005 ◽  
Vol 33 (3) ◽  
pp. 345-350 ◽  
Author(s):  
M. Balik ◽  
J. Sedivy ◽  
P. Waldauf ◽  
M. Kolar ◽  
V. Smejkalova ◽  
...  
Keyword(s):  
Fluid Balance ◽  
Total Body Water ◽  
Volume Of Distribution ◽  
Body Water ◽  
University Hospital ◽  
Pharmacokinetic Analysis ◽  
Extracellular Water ◽  
Serum Concentrations ◽  
Total Body ◽  
Volumes Of Distribution

The relationship between the volume of distribution, assessed according to the two-compartmental pharmacokinetic model, and extracellular water estimated by bioimpedance was studied in mechanically ventilated patients with sepsis and capillary leak. A prospective observational study was performed in a twenty-bed general intensive care unit in the university hospital. Patients received either vancomycin (n=16) or netilmicin (n=12) for more than 48 hours. Those with ascites, pleural effusion, on renal replacement therapy or with haemodynamic instability were excluded. Serum concentrations of drugs were taken for pharmacokinetic analysis before, 1 hour and 4 hours after the 30 minute infusion. Bioimpedance measurement was performed at the time of the third sampling. The protocol was repeated after 24 hours. Fluid balance during the 24 hour interval was recorded. Extracellular water was increased and represented 45.6 to 46.6% of total body water. Fluid balance correlated with the change of extracellular water (r=0.82, P<0.0001) and total body water (r=0.74, P<0.0001). Volumes of distribution of vancomycin (0.677±0.339 l/kg) and netilmicin (0.505±0.172 l/kg) were increased compared to normal values. A correlation was demonstrated between volume of distribution (Vdarea) of vancomycin and extra cellular water/total body ratio (r=0.70, P<0.0001). The central compartment distribution volume (V1) of netilmicin correlated with extracellular water/total body water ratio (r=0.60, P<0.003). Serum concentrations above the recommended therapeutic range were detected in 81.2% of patients on vancomycin and in 50% of patients on netilmicin. Increased volumes of distribution can be estimated by the bioimpedance measurements but are not associated with requirements for higher dosage of the glycopeptide or aminoglycoside antibiotics.

scholarly journals Pharmacokinetics of Clindamycin in Obese and Nonobese Children

2017 ◽  
Vol 61 (4) ◽  
Author(s):  
Michael J. Smith ◽  
Daniel Gonzalez ◽  
Jennifer L. Goldman ◽  
Ram Yogev ◽  
Janice E. Sullivan ◽  
...  
Keyword(s):  
Total Body Weight ◽  
The United States ◽  
Volume Of Distribution ◽  
Model Parameters ◽  
Obese Children ◽  
Obesity Status ◽  
Postmenstrual Age ◽  
Total Body ◽  
Using Data ◽  
Require Dose

ABSTRACT Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We performed a clindamycin population PK analysis using data from three separate trials. A total of 420 samples from 220 children, 76 of whom had a body mass index greater than or equal to the 95th percentile for age, were included in the analysis. Compared to other metrics, total body weight (TBW) was the most robust measure of body size. The final model included TBW and a sigmoidal maturation relationship between postmenstrual age (PMA) and clearance (CL): CL (liters/hour) = 13.8 × (TBW/70)0.75 × [PMA2.83/(39.52.83+PMA2.83)]; volume of distribution (V) was associated with TBW, albumin (ALB), and alpha-1 acid glycoprotein (AAG): V (liters) = 63.6 × (TBW/70) × (ALB/3.3)−0.83 × (AAG/2.4)−0.25. After accounting for differences in TBW, obesity status did not explain additional interindividual variability in model parameters. Our findings support TBW-based dosing for obese and nonobese children.

Pharmacokinetics and Drug Dosing in Obese Children

2010 ◽  
Vol 15 (2) ◽  
pp. 94-109
Author(s):  
Jennifer G. Kendrick ◽  
Roxane R. Carr ◽  
Mary H. H. Ensom
Keyword(s):  
Body Weight ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Drug Dose ◽  
Normal Weight ◽  
Obese Children ◽  
Physiochemical Properties ◽  
Drug Dosing ◽  
Hydrophilic Drugs ◽  
Total Body

ABSTRACT OBJECTIVES To review pharmacokinetics in obese children and to provide medication dosing recommendations. METHODS EMBASE, MEDLINE, and International Pharmaceutical Abstracts databases were searched using the following terms: obesity, morbid obesity, overweight, pharmacokinetics, drug, dose, kidney function test, creatinine, pediatric, and child. RESULTS We identified 10 studies in which the authors examined drug dosing or pharmacokinetics for obese children. No information was found for drug absorption or metabolism. Obese children have a higher percent fat mass and a lower percent lean mass compared with normal-weight children. Therefore, in obese children, the volume of distribution of lipophilic drugs is most likely higher, and that of hydrophilic drugs is most likely lower, than in normal-weight children. Serum creatinine concentrations are higher in obese than normal-weight children. Total body weight is an appropriate size descriptor for calculating doses of antineoplastics, cefazolin, and succinylcholine in obese children. Initial tobramycin doses may be determined using an adjusted body weight, although using total body weight in the context of monitoring serum tobramycin concentrations would also be an appropriate strategy. We found no information for any of the opioids; antibiotics such as penicillins, carbapenems, vancomycin, and linezolid; antifungals; cardiac drugs such as digoxin and amiodarone; corticosteroids; benzodiazepines; and anticonvulsants. In particular, we found no information about medications that are widely distributed to adipose tissue or that can accumulate there. CONCLUSIONS The available data are limited because of the small numbers of participating children, study design, or both. The number and type of drugs that have been studied limit our understanding of the pharmacokinetics in obese children. In the absence of dosing information for obese children, it is important to consider the nature and severity of a child's illness, comorbidities, organ function, and side effects and physiochemical properties of the drug. Extrapolating from available adult data is possible, as long as practitioners consider the effects of growth and development on the pharmacokinetics relevant to the child's age.

scholarly journals Disposition of intravenous metronidazole in Asian surgical patients.

1996 ◽  
Vol 40 (10) ◽  
pp. 2248-2251 ◽  
Author(s):  
T Y Ti ◽  
H S Lee ◽  
Y M Khoo
Keyword(s):  
Half Life ◽  
Inverse Correlation ◽  
Volume Of Distribution ◽  
Population Based ◽  
Surgical Patients ◽  
Pharmacokinetic Analysis ◽  
Elimination Half Life ◽  
Elimination Half ◽  
The Mean ◽  
Total Body

Steady-state peak and trough concentrations of metronidazole and its metabolites were measured in the sera of 54 surgical patients who were on intravenous metronidazole, 500 mg every 8 h. These patients had no significant renal or hepatic impairment. High-pressure liquid chromatography was used to determine the concentrations of metronidazole and its metabolites. The mean peak and trough metronidazole concentrations were 28.9 +/- 11.0 and 18.0 +/- 9.9 micrograms/ml, respectively. The acid metabolite was not detectable in all the blood specimens. The mean peak concentration of the hydroxy metabolite (MH) was 6.6 +/- 4.3 micrograms/ml, the mean trough concentration of MH was 6.2 +/- 4.2 micrograms/ml, and the MH concentration/metronidazole concentration ratio was 0.4 +/- 0.24. Using a population-based method for the pharmacokinetic analysis and stepwise regression between parameters and covariables (sex, age, and weight), we found that weight showed the highest correlation with the total body clearance (CL). The mean CL was 0.89 +/- 0.3 ml min-1 kg-1 (3.029 liters/h), the mean volume of distribution was 0.73 +/- 0.14 liter/kg, and the mean elimination half-life was 10.6 +/- 4.5 h. For the patients in our study, the CL was lower and the elimination half-life was longer compared with those for healthy volunteers, but the values of these parameters were comparable to those found for hospitalized patients. There was an inverse correlation between age and CL.

scholarly journals O35 Midazolam pharmacokinetics in children with obesity

2019 ◽  
Vol 104 (6) ◽  
pp. e15.2-e16
Author(s):  
C Gade ◽  
E Sverrisdóttir ◽  
K Dalhoff ◽  
J Sonne ◽  
H Rolighed Christensen ◽  
...  
Keyword(s):  
Body Weight ◽  
Status Epilepticus ◽  
Intravenous Administration ◽  
Plasma Concentrations ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Convulsive Status Epilepticus ◽  
List Type ◽  
Obese Children ◽  
Total Body

BackgroundMidazolam is a first-line drug for treatment of status epilepticus,1 2 both by buccal and intravenous administration. In children with obesity, the midazolam pharmacokinetics may be altered, and the current dosing guidelines may therefore be insufficient.The aim of the study was to investigate the pharmacokinetics of midazolam, after intravenous administration, in obese and non-obese children, aged 11–18 years.MethodsTrial subjects were divided into groups by Body Mass Standard Deviation Score (SDS). All children received 1 µg midazolam administered an intravenous bolus dose. Thirteen blood samples were collected per participant at prespecified timepoints over 9 hours. Plasma concentration-time data was fitted to pharmacokinetic models using non-linear mixed effects modelling (NONMEM, 7.4).ResultsSeventy-two children were enrolled in the study, of these 67 children were included in the analysis. The pharmacokinetics of midazolam was best described with a two-compartment model. The changes in pharmacokinetics in children with obesity were best described with a linear function of BMI SDS on inter-compartmental clearance and peripheral volume. Thus, the rate of distribution was faster, and the peripheral volume of distribution was larger in children with obesity as compared to non-obese children. Simulations revealed that long-term infusions based on total body weight, could lead to high plasma concentrations in children with obesity. Furthermore, simulated plasma concentrations after a fixed buccal dose showed that children with obesity may be at risk of subtherapeutic plasma concentrations.ConclusionBMI SDS was shown to have a significant influence on the peripheral volume of distribution and the inter-compartmental clearance of midazolam. The current Danish dosing guidelines for status epilepticus (http://www.paediatri.dk), where midazolam dose is adjusted to total body weight or age, may lead to both supra- and subtherapeutic doses respectively, in children with obesity. However, confirmatory studies are needed.ReferencesSmith R, Brown J. Midazolam for status epilepticus. Aust Prescr. februar 2017;40(1):23–5.Ulvi H, Yoldas T, Müngen B, Yigiter R. Continuous infusion of midazolam in the treatment of refractory generalized convulsive status epilepticus. Neurol Sci Off J Ital Neurol Soc Ital Soc Clin Neurophysiol oktober 2002;23(4):177–82.Disclosure(s)Nothing to disclose

Toxicokinetics of Colchicine in Humans: Analysis of Tissue, Plasma and Urine Data in Ten Cases

1992 ◽  
Vol 11 (6) ◽  
pp. 510-516 ◽  
Author(s):  
M. Rochdi ◽  
A. Sabouraud ◽  
F.J. Baud ◽  
C. Bismuth ◽  
J.M. Scherrmann
Keyword(s):  
Apparent Volume ◽  
Volume Of Distribution ◽  
Pharmacokinetic Analysis ◽  
Post Mortem ◽  
Elimination Half ◽  
High Concentrations ◽  
Human Poisoning ◽  
Total Body ◽  
Therapeutic Doses ◽  
Kinetics Of

1 A specific and sensitive radioimmunoassay was used to study the toxicokinetics of colchicine in seven cases of acute human poisoning. Post-mortem tissue concentrations of colchicine were measured in three further cases. Depending on the time of patient admission, two disposition processes could be observed. The first, in three patients, admitted early, showed a bi-exponential plasma colchicine decrease, with distribution half-lives of 30, 45 and 90 min. The second, in four patients, admitted late, showed a mono-exponential decrease. Plasma terminal half-lives ranged from 10.6 to 31.7 h for both groups. 2 Pharmacokinetic analysis of urine colchicine data was performed for two patients. The fraction of unchanged colchicine excreted in urine was about 30%, renal clearance was about 131 h-1 and three-fold less than total body clearance (391 h-1). The apparent volume of distribution was 211 kg-1. 3 Post-mortem tissue analysis showed an ubiquitous colchicine distribution. Colchicine accumulated at high concentrations in the bone marrow (more than 600 ng g-1), testicle (400 ng g-1), spleen (250 ng g-1), kidney (200 ng g-1), lung (200 ng g-1) and heart (95 ng g -1); it was also found in the brain (125 ng g-1). 4 This toxicokinetic study shows that after massive ingestion, the disposition parameters and kinetics of colchicine are not markedly modified from those occuring in healthy volunteers. The absorption process was not delayed and the distribution and elimination half-lives were in the range known to occur with therapeutic doses.

scholarly journals Assessing the Association Between Nutritional Status, Caries, and Gingivitis in Schoolchildren: A Cross-Sectional Study

2021 ◽  
Vol 8 ◽  
pp. 2333794X2110012
Author(s):  
Mariane C.F. Barbosa ◽  
Caio L.B. Reis ◽  
Célia M.C.F. Lopes ◽  
Isabela R. Madalena ◽  
Erika C. Küchler ◽  
...  
Keyword(s):  
Nutritional Status ◽  
International System ◽  
Cross Sectional Study ◽  
Overweight And Obesity ◽  
Dietary Habit ◽  
Overweight Children ◽  
Obese Children ◽  
Cross Sectional ◽  
Periodontal Index ◽  
Community Periodontal Index

Objective. To evaluate if nutritional status is associated with caries and gingivitis in Brazilian schoolchildren. Material and methods. Children of both genders, age ranging from 8 to 11 years old, were included in this study. Caries was diagnosed using ICDAS (International System for Detection and Assessment of Carious Lesions) and gingivitis was diagnosed using the Community Periodontal Index. The nutritional status of each child was defined by BMI Z-score calculation. Data on oral health behavior and dietary habit were collected through parent’s questionnaires. Parametric analyzes were performed to compare the groups. The established alpha was 5%. Results. The sample consisted of 353 schoolchildren: 16 underweight children, 247 eutrophic children, 64 overweight children, and 26 were obese children. Overweight, Obese and Overweight + Obese children presented less cavitated caries lesion than Eutrophic children ( P < .05). Gingivitis was not associated with nutritional status ( P > .05). Conclusion. Caries was associated with overweight and obesity in Brazilian schoolchildren.

The Role of Obesity in Motor Vehicle Injuries and Fatalities in the Pediatric Population: A Systematic Review

2021 ◽  
pp. 088506662199273
Author(s):  
Zana Alattar ◽  
Shelby Hoebee ◽  
Eyal Ron ◽  
Paul Kang ◽  
Eric vanSonnenberg
Keyword(s):  
Systematic Review ◽  
Risk Factor ◽  
Motor Vehicle ◽  
Pediatric Population ◽  
Extremity Injury ◽  
Obese Children ◽  
Patients Âgés ◽  
Vehicle Accidents ◽  
Increased Risk ◽  
Extremity Injuries

Purpose: A systematic review done to evaluate obesity as a risk factor for injuries and mortality in motor vehicle accidents (MVAs) in the pediatric population, as there has not been a systematic review done in over 10 years. This study aims to update the literature regarding obesity as a risk factor for injuries in MVAs in the pediatric population. Materials and Methods: A systematic review was conducted according to the PRISMA guidelines with strict inclusion and exclusion criteria, resulting in the use of 3 total articles to analyze obesity as a risk factor for overall injury and mortality in the pediatric population. Results: Zaveri et al demonstrated a statistically significant, but weak, decrease in the odds of extremity injury in overweight patients ages 2 to 17 years old (odds ratio [OR] = 0.6, 95% confidence interval [CI] = 0.4-1.0, P ≤ 0.05). On the other hand, Pollack et al and Haricharan et al found an increase in extremity injury in the obese population, in ages 9 to 15 years (OR = 2.54, 95% CI = 1.15-5.59, P ≤ 0.05), and 10 to 17 years (Age 10-13: OR = 6.06, 95% CI = 2.23-16.44, P ≤ 0.05, Age 14-17 OR = 1.44, 95% CI = 1.04-2.00, P ≤ 0.05), respectively. Haricharan et al also found an increase in thoracic injuries in obese children, ages 2 to 13 and increased risk of head/face/neck injury in obese children ages 2 to 5 (OR = 3.67, 95% CI = 1.03-13.08, P ≤ 0.05), but a decreased risk of head injury in obese children ages 14 to 17 (OR = 0.33, 95% CI = 0.18-0.60, P ≤ 0.05). Conclusions: There are sparse data that are conflicting, regarding the effect of obesity on extremity injuries in the pediatric population. Obesity is not protective against thoracic, head, or abdominal injuries. However, it was found to be a risk factor for trunk injuries in ages 2 to 13, as well as head/face/neck injuries for ages 2 to 5. Since the literature is so sparse, further research is warranted in these areas.

scholarly journals Comparable Population Pharmacokinetics and Pharmacodynamic Breakpoints of Cefpirome in Cystic Fibrosis Patients and Healthy Volunteers

2011 ◽  
Vol 55 (6) ◽  
pp. 2927-2936 ◽  
Author(s):  
J. B. Bulitta ◽  
M. Kinzig ◽  
C. B. Landersdorfer ◽  
U. Holzgrabe ◽  
U. Stephan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Healthy Volunteers ◽  
High Performance ◽  
Standard Dose ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Nonparametric Bootstrap ◽  
Population Pk ◽  
Total Body ◽  
Similar Body

ABSTRACTCystic fibrosis (CF) patients are often reported to have higher clearances and larger volumes of distribution per kilogram of total body weight (WT) for beta-lactams than healthy volunteers. As pharmacokinetic (PK) data on cefpirome from studies of CF patients are lacking, we systematically compared its population PK and pharmacodynamic breakpoints for CF patients and healthy volunteers of similar body size. Twelve adult CF patients (median lean body mass [LBM] = 45.7 kg) and 12 healthy volunteers (LBM = 50.0 kg) received a single 10-min intravenous infusion of 2 g cefpirome. Plasma and urine concentrations were determined by high-performance liquid chromatography (HPLC). Population PK and Monte Carlo simulations were performed using NONMEM and S-ADAPT and a duration of an unbound plasma concentration above the MIC ≥ 65% of the dosing interval as a pharmacodynamic target. Unscaled clearances for CF patients were similar to those seen with healthy volunteers, and the volume of distribution was 6% lower for CF patients. Linear scaling of total clearance by WT resulted in clearance that was 20% higher (P≤ 0.001 [nonparametric bootstrap]) in CF patients. Allometric scaling by LBM explained the differences between the two subject groups with respect to average clearance and volume of distribution and reduced the unexplained between-subject variability of renal and nonrenal clearance by 10 to 14%. For the CF patients, robust (>90%) probabilities of target attainment (PTA) were achieved by the administration of a standard dose of 2 g/70 kg WT every 12 h (Q12h) given as 30-min infusions for MICs ≤ 1.5 mg/liter. As alternative dosage regimens, a 5-h infusion of 1.33 g/70 kg WT Q8h achieved robust PTAs for MICs ≤ 8 to 12 mg/liter and a continuous infusion of 4 g/day for MICs ≤ 12 mg/liter. Prolonged infusion of cefpirome is expected to be superior to short-term infusions for MICs between 2 and 12 mg/liter.

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