Effects of Prenatal Exposure to Betamethasone and Indomethacin on the Glomerular Filtration Rate in the Preterm Infant

Anker, John N. van den; Hop, W. C. J.; Groot, Ronald de; Heijden, Bert J. van der; Broerse, H. M.; Lindemans, Jan; Sauer, Pieter

doi:10.1203/00006450-199411000-00006

Cited by 70 publications

(31 citation statements)

References 18 publications

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“…Van den Anker et al have reported on the impact of maternal administration of betamethasone before birth on inulin clearance on days 3 and 10 of postnatal life [32]. We were unable to confirm these observations in either a population PK study on maturation of amikacin pharmacokinetics (24-30 weeks PMA at birth) or in the current study examining the first month of life.…”

Section: Discussioncontrasting

confidence: 56%

Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance

Anderson

Allegaert

Anker

et al. 2006

Brit J Clinical Pharma

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: Discussioncontrasting

confidence: 56%

Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance

Anderson

Allegaert

Anker

et al. 2006

Brit J Clinical Pharma

151

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“…Nephrogenesis is complete at 34 weeks of gestation although growth retardation, nephrotoxic drugs administered during pregnancy and congenital renal malformations can have a negative effect on kidney development [57,58]. Drugs that affect kidney function, such as ibuprofen, given in the neonatal period can have ongoing effects beyond the period of administration [59,60].…”

Section: Excretionmentioning

confidence: 99%

Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future

O’Hara

Wright

Schneider

et al. 2015

Brit J Clinical Pharma

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Paediatric patients, particularly preterm neonates, present many pharmacological challenges. Due to the difficulty in conducting clinical trials in these populations dosing information is often extrapolated from adult populations. As the processes of absorption, distribution, metabolism and excretion of drugs change throughout growth and development extrapolation presents risk of over or underestimating the doses required. Information about the development these processes, particularly drug metabolism pathways, is still limited with weight based dose adjustment presenting the best method of estimating pharmacokinetic changes due to growth and development. New innovations in pharmacokinetic research, such as population pharmacokinetic modelling, present unique opportunities to conduct clinical trials in these populations improving the safety and effectiveness of the drugs used. More research is required into this area to ensure the best outcomes for our most vulnerable patients.

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“…after birth by means of the continuous inulin infusion technique (6,7). A 10% glucose-inulin solution cont aining 25 g of inulin per liter was infused at a rate of 0.6 mL/kglh , beginning at time (t) zero of the pharm acokinetic study .…”

Section: Patientsmentioning

confidence: 99%

The Effect of Asphyxia on the Pharmacokinetics of Ceftazidime in the Term Newborn

et al. 1995

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Vol. 38, No. 5, 1995 Printed ill U.S.A.ml.zh), CAZ clearance per kg (40.9 ± 6.1 mLih/kg versus 60.8 ± 8.3 mLih/kg), and the GFR expressed in mLimin (3.14 ± 0.43 versus 4.73 ± 0.89) were significantly (p < 0.001) decreased in the asphyxiated newborn. We conclud e that twice daily administration of 50 rug/kg of body weight CAZ given to asphyxiated term newborns in the first days of life results in significantly higher serum trough levels in comparison with control infants. The impaired CAZ clea rance is a result of a significantly decreased GFR. Perinat al asphyxia is a result of complicated or traumatic deliveries and may exert profound effects on renal and liver function. McCance and Widd owson (1) reported as early as 1954 a reducti on in the GFR, a poor urea clearance , and a low urine output in full-term and postmature infants after prolonged and difficult labor. A redistribution of the fetal circulation leading to an increas ed blood flow to the brain, heart, and adrenals and a concomitantly decrea sed blood flow to the lungs, intestines, and kidneys is responsi ble for this asphyxiainduced renal impairment (2). Several drugs such as the f3-l actam antibiotic CAZ are primar ily excrete d by the kidneys. CAZ, a broad spectrum cephalosporin, is an antibiotic frequentl y used for the treatment of infectious diseases in newborn infants. The currently recommended dosage for CAZ in term infants is 50-150 mglkg of body weight per day in two or

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Effects of Prenatal Exposure to Betamethasone and Indomethacin on the Glomerular Filtration Rate in the Preterm Infant

Cited by 70 publications

References 18 publications

Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance

Vancomycin pharmacokinetics in preterm neonates and the prediction of adult clearance

Pharmacokinetics in neonatal prescribing: evidence base, paradigms and the future

The Effect of Asphyxia on the Pharmacokinetics of Ceftazidime in the Term Newborn

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