When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers?
Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs....
Ausführliche Beschreibung
Autor*in: |
Wu, Yunjiao [verfasserIn] Allegaert, Karel [verfasserIn] Flint, Robert B. [verfasserIn] Goulooze, Sebastiaan C. [verfasserIn] Välitalo, Pyry A. J. [verfasserIn] de Hoog, Matthijs [verfasserIn] Mulla, Hussain [verfasserIn] Sherwin, Catherine M. T. [verfasserIn] Simons, Sinno H. P. [verfasserIn] Krekels, Elke H. J. [verfasserIn] Knibbe, Catherijne A. J. [verfasserIn] Völler, Swantje [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2024 |
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Schlagwörter: |
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Anmerkung: |
© The Author(s) 2024 |
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Übergeordnetes Werk: |
Enthalten in: Pharmaceutical research - Springer US, 1984, 41(2024), 4 vom: 12. März, Seite 637-649 |
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Übergeordnetes Werk: |
volume:41 ; year:2024 ; number:4 ; day:12 ; month:03 ; pages:637-649 |
Links: |
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DOI / URN: |
10.1007/s11095-024-03677-3 |
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Katalog-ID: |
SPR055555969 |
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520 | |a Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. | ||
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650 | 4 | |a glomerular filtration rate |7 (dpeaa)DE-He213 | |
650 | 4 | |a inulin clearance |7 (dpeaa)DE-He213 | |
650 | 4 | |a maturation |7 (dpeaa)DE-He213 | |
650 | 4 | |a preterm neonates |7 (dpeaa)DE-He213 | |
700 | 1 | |a Allegaert, Karel |e verfasserin |4 aut | |
700 | 1 | |a Flint, Robert B. |e verfasserin |4 aut | |
700 | 1 | |a Goulooze, Sebastiaan C. |e verfasserin |4 aut | |
700 | 1 | |a Välitalo, Pyry A. J. |e verfasserin |4 aut | |
700 | 1 | |a de Hoog, Matthijs |e verfasserin |4 aut | |
700 | 1 | |a Mulla, Hussain |e verfasserin |4 aut | |
700 | 1 | |a Sherwin, Catherine M. T. |e verfasserin |4 aut | |
700 | 1 | |a Simons, Sinno H. P. |e verfasserin |4 aut | |
700 | 1 | |a Krekels, Elke H. J. |e verfasserin |4 aut | |
700 | 1 | |a Knibbe, Catherijne A. J. |e verfasserin |4 aut | |
700 | 1 | |a Völler, Swantje |e verfasserin |0 (orcid)0000-0003-0587-2775 |4 aut | |
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10.1007/s11095-024-03677-3 doi (DE-627)SPR055555969 (SPR)s11095-024-03677-3-e DE-627 ger DE-627 rakwb eng 610 VZ PHARM DE-84 fid 15,3 ssgn 44.38 bkl Wu, Yunjiao verfasserin aut When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. creatinine (dpeaa)DE-He213 glomerular filtration rate (dpeaa)DE-He213 inulin clearance (dpeaa)DE-He213 maturation (dpeaa)DE-He213 preterm neonates (dpeaa)DE-He213 Allegaert, Karel verfasserin aut Flint, Robert B. verfasserin aut Goulooze, Sebastiaan C. verfasserin aut Välitalo, Pyry A. J. verfasserin aut de Hoog, Matthijs verfasserin aut Mulla, Hussain verfasserin aut Sherwin, Catherine M. T. verfasserin aut Simons, Sinno H. P. verfasserin aut Krekels, Elke H. J. verfasserin aut Knibbe, Catherijne A. J. verfasserin aut Völler, Swantje verfasserin (orcid)0000-0003-0587-2775 aut Enthalten in Pharmaceutical research Springer US, 1984 41(2024), 4 vom: 12. März, Seite 637-649 (DE-627)325485291 (DE-600)2036232-8 1573-904X nnns volume:41 year:2024 number:4 day:12 month:03 pages:637-649 https://dx.doi.org/10.1007/s11095-024-03677-3 X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 VZ AR 41 2024 4 12 03 637-649 |
spelling |
10.1007/s11095-024-03677-3 doi (DE-627)SPR055555969 (SPR)s11095-024-03677-3-e DE-627 ger DE-627 rakwb eng 610 VZ PHARM DE-84 fid 15,3 ssgn 44.38 bkl Wu, Yunjiao verfasserin aut When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. creatinine (dpeaa)DE-He213 glomerular filtration rate (dpeaa)DE-He213 inulin clearance (dpeaa)DE-He213 maturation (dpeaa)DE-He213 preterm neonates (dpeaa)DE-He213 Allegaert, Karel verfasserin aut Flint, Robert B. verfasserin aut Goulooze, Sebastiaan C. verfasserin aut Välitalo, Pyry A. J. verfasserin aut de Hoog, Matthijs verfasserin aut Mulla, Hussain verfasserin aut Sherwin, Catherine M. T. verfasserin aut Simons, Sinno H. P. verfasserin aut Krekels, Elke H. J. verfasserin aut Knibbe, Catherijne A. J. verfasserin aut Völler, Swantje verfasserin (orcid)0000-0003-0587-2775 aut Enthalten in Pharmaceutical research Springer US, 1984 41(2024), 4 vom: 12. März, Seite 637-649 (DE-627)325485291 (DE-600)2036232-8 1573-904X nnns volume:41 year:2024 number:4 day:12 month:03 pages:637-649 https://dx.doi.org/10.1007/s11095-024-03677-3 X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 VZ AR 41 2024 4 12 03 637-649 |
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10.1007/s11095-024-03677-3 doi (DE-627)SPR055555969 (SPR)s11095-024-03677-3-e DE-627 ger DE-627 rakwb eng 610 VZ PHARM DE-84 fid 15,3 ssgn 44.38 bkl Wu, Yunjiao verfasserin aut When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. creatinine (dpeaa)DE-He213 glomerular filtration rate (dpeaa)DE-He213 inulin clearance (dpeaa)DE-He213 maturation (dpeaa)DE-He213 preterm neonates (dpeaa)DE-He213 Allegaert, Karel verfasserin aut Flint, Robert B. verfasserin aut Goulooze, Sebastiaan C. verfasserin aut Välitalo, Pyry A. J. verfasserin aut de Hoog, Matthijs verfasserin aut Mulla, Hussain verfasserin aut Sherwin, Catherine M. T. verfasserin aut Simons, Sinno H. P. verfasserin aut Krekels, Elke H. J. verfasserin aut Knibbe, Catherijne A. J. verfasserin aut Völler, Swantje verfasserin (orcid)0000-0003-0587-2775 aut Enthalten in Pharmaceutical research Springer US, 1984 41(2024), 4 vom: 12. März, Seite 637-649 (DE-627)325485291 (DE-600)2036232-8 1573-904X nnns volume:41 year:2024 number:4 day:12 month:03 pages:637-649 https://dx.doi.org/10.1007/s11095-024-03677-3 X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 VZ AR 41 2024 4 12 03 637-649 |
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10.1007/s11095-024-03677-3 doi (DE-627)SPR055555969 (SPR)s11095-024-03677-3-e DE-627 ger DE-627 rakwb eng 610 VZ PHARM DE-84 fid 15,3 ssgn 44.38 bkl Wu, Yunjiao verfasserin aut When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. creatinine (dpeaa)DE-He213 glomerular filtration rate (dpeaa)DE-He213 inulin clearance (dpeaa)DE-He213 maturation (dpeaa)DE-He213 preterm neonates (dpeaa)DE-He213 Allegaert, Karel verfasserin aut Flint, Robert B. verfasserin aut Goulooze, Sebastiaan C. verfasserin aut Välitalo, Pyry A. J. verfasserin aut de Hoog, Matthijs verfasserin aut Mulla, Hussain verfasserin aut Sherwin, Catherine M. T. verfasserin aut Simons, Sinno H. P. verfasserin aut Krekels, Elke H. J. verfasserin aut Knibbe, Catherijne A. J. verfasserin aut Völler, Swantje verfasserin (orcid)0000-0003-0587-2775 aut Enthalten in Pharmaceutical research Springer US, 1984 41(2024), 4 vom: 12. März, Seite 637-649 (DE-627)325485291 (DE-600)2036232-8 1573-904X nnns volume:41 year:2024 number:4 day:12 month:03 pages:637-649 https://dx.doi.org/10.1007/s11095-024-03677-3 X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 VZ AR 41 2024 4 12 03 637-649 |
allfieldsSound |
10.1007/s11095-024-03677-3 doi (DE-627)SPR055555969 (SPR)s11095-024-03677-3-e DE-627 ger DE-627 rakwb eng 610 VZ PHARM DE-84 fid 15,3 ssgn 44.38 bkl Wu, Yunjiao verfasserin aut When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? 2024 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2024 Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. creatinine (dpeaa)DE-He213 glomerular filtration rate (dpeaa)DE-He213 inulin clearance (dpeaa)DE-He213 maturation (dpeaa)DE-He213 preterm neonates (dpeaa)DE-He213 Allegaert, Karel verfasserin aut Flint, Robert B. verfasserin aut Goulooze, Sebastiaan C. verfasserin aut Välitalo, Pyry A. J. verfasserin aut de Hoog, Matthijs verfasserin aut Mulla, Hussain verfasserin aut Sherwin, Catherine M. T. verfasserin aut Simons, Sinno H. P. verfasserin aut Krekels, Elke H. J. verfasserin aut Knibbe, Catherijne A. J. verfasserin aut Völler, Swantje verfasserin (orcid)0000-0003-0587-2775 aut Enthalten in Pharmaceutical research Springer US, 1984 41(2024), 4 vom: 12. März, Seite 637-649 (DE-627)325485291 (DE-600)2036232-8 1573-904X nnns volume:41 year:2024 number:4 day:12 month:03 pages:637-649 https://dx.doi.org/10.1007/s11095-024-03677-3 X:VERLAG 0 kostenfrei Volltext SYSFLAG_0 GBV_SPRINGER FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.38 VZ AR 41 2024 4 12 03 637-649 |
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Enthalten in Pharmaceutical research 41(2024), 4 vom: 12. März, Seite 637-649 volume:41 year:2024 number:4 day:12 month:03 pages:637-649 |
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Enthalten in Pharmaceutical research 41(2024), 4 vom: 12. März, Seite 637-649 volume:41 year:2024 number:4 day:12 month:03 pages:637-649 |
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creatinine glomerular filtration rate inulin clearance maturation preterm neonates |
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Wu, Yunjiao @@aut@@ Allegaert, Karel @@aut@@ Flint, Robert B. @@aut@@ Goulooze, Sebastiaan C. @@aut@@ Välitalo, Pyry A. J. @@aut@@ de Hoog, Matthijs @@aut@@ Mulla, Hussain @@aut@@ Sherwin, Catherine M. T. @@aut@@ Simons, Sinno H. P. @@aut@@ Krekels, Elke H. J. @@aut@@ Knibbe, Catherijne A. J. @@aut@@ Völler, Swantje @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000naa a22002652 4500</leader><controlfield tag="001">SPR055555969</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20240418064739.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">240418s2024 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1007/s11095-024-03677-3</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR055555969</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s11095-024-03677-3-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">PHARM</subfield><subfield code="q">DE-84</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">15,3</subfield><subfield code="2">ssgn</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.38</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Wu, Yunjiao</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers?</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2024</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s) 2024</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. 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|
author |
Wu, Yunjiao |
spellingShingle |
Wu, Yunjiao ddc 610 fid PHARM ssgn 15,3 bkl 44.38 misc creatinine misc glomerular filtration rate misc inulin clearance misc maturation misc preterm neonates When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? |
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Wu, Yunjiao |
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electronic Article |
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610 - Medicine & health |
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1573-904X |
topic_title |
610 VZ PHARM DE-84 fid 15,3 ssgn 44.38 bkl When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? creatinine (dpeaa)DE-He213 glomerular filtration rate (dpeaa)DE-He213 inulin clearance (dpeaa)DE-He213 maturation (dpeaa)DE-He213 preterm neonates (dpeaa)DE-He213 |
topic |
ddc 610 fid PHARM ssgn 15,3 bkl 44.38 misc creatinine misc glomerular filtration rate misc inulin clearance misc maturation misc preterm neonates |
topic_unstemmed |
ddc 610 fid PHARM ssgn 15,3 bkl 44.38 misc creatinine misc glomerular filtration rate misc inulin clearance misc maturation misc preterm neonates |
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ddc 610 fid PHARM ssgn 15,3 bkl 44.38 misc creatinine misc glomerular filtration rate misc inulin clearance misc maturation misc preterm neonates |
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Elektronische Aufsätze Aufsätze Elektronische Ressource |
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When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? |
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Wu, Yunjiao Allegaert, Karel Flint, Robert B. Goulooze, Sebastiaan C. Välitalo, Pyry A. J. de Hoog, Matthijs Mulla, Hussain Sherwin, Catherine M. T. Simons, Sinno H. P. Krekels, Elke H. J. Knibbe, Catherijne A. J. Völler, Swantje |
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when will the glomerular filtration rate in former preterm neonates catch up with their term peers? |
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When will the Glomerular Filtration Rate in Former Preterm Neonates Catch up with Their Term Peers? |
abstract |
Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. © The Author(s) 2024 |
abstractGer |
Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. © The Author(s) 2024 |
abstract_unstemmed |
Aims Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs. Methods We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of $ GFR_{birth} $ (GFR at birth), and an Emax model dependent on PNA (with $ GFR_{max} $, $ PNA_{50} $ (PNA at which half of $${GFR}_{max}$$ is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations. Result In the GFR model, $ GFR_{birth} $ varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for $ PNA_{50} $, and current weight for $ GFR_{max} $. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well. Conclusions GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age. © The Author(s) 2024 |
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score |
7.4001093 |