Inulin Clearance in the Newborn Infant: Relationship to Gestational and Postnatal Age

Leake, Rosemary D.; Trygstad, Carl W.; Oh, William

doi:10.1203/00006450-197608000-00013

Cited by 62 publications

(45 citation statements)

References 5 publications

(7 reference statements)

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“…PNA and GA are known predictors of glomerular filtration rate (GFR) maturation and drug Cl. 15,24,25 TEMP being an independent covariate is very interesting. It can be debated that PNA (reflecting GFR maturation and drug Cl) and TEMP are correlated and a distinction in the effect of both on Cl is not possible.…”

Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia

Bijleveld

Mathôt

Lee

et al. 2017

Clin Pharma and Therapeutics

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The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N 5 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.58C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.08C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively. Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? þ To date, there are no data on the effect of moderate hypothermia on the pharmacokinetics (PK) of amoxicillin in term neonates. Only few studies have been performed to evaluate the PK of this antibiotic in noncooled (pre)term neonates. WHAT QUESTION DID THIS STUDY ADDRESS? þ To our knowledge, this is the first prospective study evaluating and describing the PK of amoxicillin during all phases of controlled hypothermia in newborns, e.g., the hypothermic, rewarming, and normothermic phases.WHAT THIS STUDY ADDS TO OUR KNOWLEDGE þ A description of the PK properties of amoxicillin in term newborns with hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia receiving hypothermia treatment. Gestational age (GA), postnatal age (PNA), urine output, and body temperature were significant covariates on amoxicillin clearance (Cl). HOW THIS MIGHT CHANGE CLINICAL PHARMA-COLOGY OR TRANSLATIONAL SCIENCE þ Based on the newly developed PK-model, we advise an amoxicillin dosing regimen of 50 or 75 mg/kg/24h in three doses for patients with GA 36 or GA 38-42 weeks, respectively.Term neonates who experience a severe hypoxic-ischemic insult during birth and develop encephalopathy are treated with hypothermia.1,2 This improves long-term outcomes and reduces mortality rates.2-9 These patients may suffer from early-onset sepsis with Streptococcus agalactiae (incidence rate 0.43% (95% confidence interval (CI) 0.37-0.49)), while Listeria monocytogenes should also be considered.10 Because asphyxia due to infection is difficult to distinguish from asphyxia without infection, antibiotics, such as amoxicillin, are frequently used.11 For efficacy, as a surrogate marker, the time that the nonprotein-bound concentration in blood exceeds the minimum inhibitory concentration (T>MIC) should be at least 40-50% in these patients.12 Although b-lactam antibiotics such as amoxicillin are considered safe due to the wide therapeutic range, excessive accumulation can lead to the development of adverse drug events, such as seizures and crystalluria. 13Despi...

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Section: Discussionmentioning

confidence: 99%

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia

Bijleveld

Mathôt

Lee

et al. 2017

Clin Pharma and Therapeutics

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“…Three-quarters of ml of whole blood was obtained by heel puncture, 45 min after the onset of the inulin infusion for plasma inulin (13) and creatinine. To minimize the quantity of the total whole blood drawn from these infants, one sample was taken for inulin; it has been previously shown that low birthweight infants reach a serum steady-state for inulin 45 min after the onset of the infusion (13). Serum bilirubin was measured in 26 studies (14).…”

Section: Materials a N D Methodsmentioning

confidence: 99%

Validity of Endogenous Creatinine Clearance in Low Birthweight Infants

Stonestreet

Bell

1979

Pediatr Res

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SummaryDespite methodologic problems, endogenous creatinine clearance is commonly used as an estimation-of glomerular filtration rate (GFR). lnulin clearance was compared to endogenous creatinine clearance in a group of low birthweight infants to establish the validity of the latter. Thirty-three low birthweight infants (birthweight mean = 1600 g, gestational age mean = 33 wk) were studied between 10 hr and 10 days of age to simultaneously measure GFR by inulin and endogenous creatinine clearances.Inulin and creatinine clearances correlated directly (r = 0.738, P > 0.001). The slope of the regression line suggested an overestimation of GFR (inulin clearance) by creatinine clearance a t the low GFR range and an underestimation at the high GFR range. The data were divided into two groups by the median inulin clearance (12.5 ml/min/1.73mz). The ratio of creatinine to inulin clearance was significantly higher in the low GFR group (1.28 2 0.16 vs. 0.89 + 0.04 SEM, n = 19, P < 0.05). There was no difference between the two groups in plasma creatinine, birthweight, gestational age, incidence of respiratory distress, or oxygen requirements a t the time of the studies. Endogenous creatinine clearance represents a good estimation of GFR (inulin clearance) in low birthweight infants. However, at the low GFR range, it represents an overestimation and at the high GFR range, an underestimation. SpeculationIn low birthweight infants, tubular secretion of creatinine and plasma chromogens interfere with the accuracy of endogenous creatinine clearance. Tubular secretion of creatinine is ~robablv of relatively greater importance a t lower GFR's accounting for an overestimation of GFR by creatinine clearance. At higher GFR's.plasma chromogens are probably of more importance and account, in part, for the underestimation of GFR by creatinine clearance.The validity of endogenous creatinine clearance as a measure of G F R in adults, children, and infants has long been the subject of discussions and investigations (1-3, 7, 8, 16). Despite methodologic and technical problems (I I), it remains the most commonly used laboratory aid for the assessment of glomerular functions in clinical practice. In neonates, the problekis compounded by the presence of noncreatinine interfering substances such as chromogens, including bilirubin, which may raise the plasma creatinine levels, thus, giving falsely low endogenous creatinine clearances. The Jaffe reaction (6), a commonly used method for the determination of creatinine in biologic fluids, does not exclude these interfering substances (1, 2, 6, 11). Although falsely high plasma and urinary creatinine levels may counterbalance each other in the calculation of creatinine clearance, the correlation with true G F R has not been established in low birthweight infants. The purpose of this study was to establish the correlation between endogenous creatinine and inulin clearance as a measure of G F R in low birthweight infants. MATERIALS A N D METHODSThirty-three low birthweight infants (I7 males and 16 f...

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“…GFR values were determined by means of the continuous inulin infusion technique on the third day of life (5,6,12). Inulin was obtained from Laevosan Gesellschaft mbH (Lienz, Austria) and was administered as a solution containing 25 g inulin/L at an infusion rate of 0.6 mL/kg/h.…”

Section: Patientsmentioning

confidence: 99%

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

et al. 1994

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Inulin Clearance in the Newborn Infant: Relationship to Gestational and Postnatal Age

Cited by 62 publications

References 5 publications

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia

Validity of Endogenous Creatinine Clearance in Low Birthweight Infants

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

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