Dose estimation for children

Baber, Nigel; Pritchard, Deborah

doi:10.1046/j.1365-2125.2003.01901.x

Cited by 27 publications

(17 citation statements)

References 24 publications

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“…The 'mature' estimate of CLstd 3.9 l h −1 70 kg −1 (95% confidence interval 2.76, 4.98) predicted by this variable slope sigmoidal model is similar to reported values in adults. There is currently considerable debate about the estimation of paediatric parameter estimates from adult data [34,35]. Use of a variable slope sigmoidal model may allow prediction of adult parameter estimates from premature neonatal data.…”

Section: Discussionmentioning

confidence: 99%

Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance

Anderson

Allegaert

Anker

et al. 2006

Brit J Clinical Pharma

153

151

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What is already known about this subject• Effects of size, renal function, age (postnatal age, gestational age and postmenstrual age) as predictors of vancomycin clearance in premature neonates are established, but the relative contribution of each component remains poorly quantified, largely because these variables are closely correlated.• We have quantified the covariates contributing to vancomycin clearance population parameter variability in order to establish the major covariates required for dosing predictions. Size, standardized using allometric models, was the primary covariate used in our analysis. What this study adds• Size explained 49.8%, postmenstrual age 18.2% and renal function 14.1% of clearance variability.• Descriptors of the relationship between age and clearance in premature neonates vary.• The use of a variable slope sigmoidal model to describe the relationship between clearance and postmenstrual age predicted an adult clearance of 3.79 l h − 1 70 kg − 1 (95% confidence interval 2.76, 4.98) from premature neonatal data. AimTo identify and quantify factors describing the variability of vancomycin clearance in premature neonates. MethodsPopulation pharmacokinetics were estimated (NONMEM) in 214 neonates [postmenstrual age (PMA) 30.4 weeks, range 24-34 weeks; postnatal age 11.9 days, range 1-27 days; weight 1.30 kg, range 0.42-2.6 kg] using therapeutic drug monitoring data. Covariate analysis included weight, PMA, serum creatinine, use of inotropes or ibuprofen, positive blood culture and respiratory support. A one-compartment linear disposition model with zero order input and first-order elimination was used to describe the data (604 observations). ResultsThe population estimate for volume of distribution ( V ) was 39 l 70 kg − 1 (coefficient of variation 19.4%). Clearance (CL) increased from 0.897 l h − 1 70 kg − 1 at 24 weeks PMA to 2.02 l h − 1 70 kg − 1 by 34 weeks PMA. The between-subject variability for CL was 18.6% and the between-occasion variability was 12.2%. The use of ibuprofen reduced clearance, but this effect was attributable to reduced renal function. Overall, 82% of the variability of CL was predictable. Size explained 49.8%, P MA 18.2% and renal function 14.1%. The use of a variable slope sigmoidal model to describe the relationship between clearance and PMA predicted an adult clearance of 3.79 l h − 1 70 kg − 1 (95% confidence interval 2.76, 4.98). ConclusionsSize, renal function and PMA are the major contributors to clearance variability in premature neonates. The small (18%) unexplained variability in clearance suggests target concentration intervention is unnecessary if size, age and renal function are used to predict the dose. Extrapolation to an adult clearance from neonatal data is possible using allometric size models and a function describing clearance maturation.B. J. Anderson et al.

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Section: Discussionmentioning

confidence: 99%

Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance

Anderson

Allegaert

Anker

et al. 2006

Brit J Clinical Pharma

153

151

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“…Dosing of midazolam, like most medicines used in children, is based on body weight 2–4. Dosing in children is usually extrapolated from pharmacokinetic studies in adults.…”

Section: Introductionmentioning

confidence: 99%

Inter-individual variation in midazolam clearance in children

2014

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ObjectivesTo determine the extent of inter-individual variation in clearance of midazolam in children and establish which factors are responsible for this variation.MethodsA systematic literature review was performed to identify papers describing the clearance of midazolam in children. The following databases were searched: Medline, Embase, International Pharmaceutical Abstracts, CINAHL and Cochrane Library. From the papers, the range in plasma clearance and the coefficient of variation (CV) in plasma clearance were determined.Results25 articles were identified. Only 13 studies gave the full range of clearance values for individual patients. The CV was greater in critically ill patients (18%–170%) than non-critically ill patients (13%–54%). Inter-individual variation was a major problem in all age groups of critically ill patients. The CV was 72%–106% in preterm neonates, 18%–73% in term neonates, 31%–130% in infants, 21%–170% in children and 47%–150% in adolescents. The mean clearance was higher in children (1.1–16.7 mL/min/kg) than in neonates (0.78–2.5 mL/min/kg).ConclusionsLarge inter-individual variation was seen in midazolam clearance values in critically ill neonates, infants, children and adolescents.

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“…[7] Most drug doses have been calculated using allometric scales that relate children's body weight or body surface area to the recommended adult dosage. [8] The consequences of an erroneous dose can be seen in the ineffectiveness of treatment or in the appearance of severe adverse effects or even into intoxication or deaths, for example four children under 36 months died due to suffocation when they tried swallowing albendazole tablets (too large for their age) during a deworming campaign in Ethiopia during 2007. [8] In addition, an excipient added to the formulations, to fulfill some specific function, can cause harmful results in the patients, [10,11] for example the respiratory distress syndrome observed in babies exposed to the benzyl alcohol used as preservative in solutions for injection.…”

Section: Introductionmentioning

confidence: 99%

“…[8] The consequences of an erroneous dose can be seen in the ineffectiveness of treatment or in the appearance of severe adverse effects or even into intoxication or deaths, for example four children under 36 months died due to suffocation when they tried swallowing albendazole tablets (too large for their age) during a deworming campaign in Ethiopia during 2007. [8] In addition, an excipient added to the formulations, to fulfill some specific function, can cause harmful results in the patients, [10,11] for example the respiratory distress syndrome observed in babies exposed to the benzyl alcohol used as preservative in solutions for injection. [12,13] Also, the hyperactivity due to azo dyes; activation of symptomatic in patients with gluten, lactose, fructose or galactose intolerance and potential allergies due to the presence of peanut, sesame or soya oils.…”

Section: Introductionmentioning

confidence: 99%

Quality Assessment in the Extemporaneous Pediatric Preparation of Powder Papers Containing Crushed Tablets of Spironolactone or Amiodarone

Carrillo¹,

Herrera²

2017

WJPR

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To elaborate the pediatric medicines the specifics of this population must be considered. Powder papers as extemporaneous formulations may be an option to provide dosing flexibility. The main objective of this research was to evaluate the quality of powder papers in its manual preparation stages and during the 60 days of storage. The results shown that a smaller than expected mass of tablets was distributed for the 40 papers at each formulation. The precision in the distribution performed by the crushed and pulverized tablet preparatory assistant reflected relative standard deviations ranging from 9 to 15%. On the start day, the uniformity of mass showed an inaccuracy reflected in several values outside the expected range, for all formulations. The accuracy of the tablets powder mass during storage at 60 days showed a ±10% of difference respect basal mass for papers with spironolactone 6,25 mg and the 15 and 75 mg amiodarone hydrochloride papers. For 10 mg of amiodarone hydrochloride formulation, random errors occurred outside the expected ranges at two sampling times. Powder adherence percentage was between the 10 and 20%. In conclusion, the preparation of four formulations in powder paper showed some errors which resulted in a significant loss of dose. A standardized operating procedure for the preparation of powder papers should be available taking into account the risk points of the manufacturing processes. It is advisable to enable the galenical section in hospital pharmacies and to have legislation regulating extemporaneous formulations in Costa Rica.

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Dose estimation for children

Cited by 27 publications

References 24 publications

Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance

Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance

Inter-individual variation in midazolam clearance in children

Quality Assessment in the Extemporaneous Pediatric Preparation of Powder Papers Containing Crushed Tablets of Spironolactone or Amiodarone

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