Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-Physiological Function for Maturation in Glomerular Filtration

Roosmarijn F.W. de Cock; Karel Allegaert; Janneke M. Brussee; Catherine M.T. Sherwin; Hussain Mulla; Matthijs de Hoog; John N. van den Anker; Meindert Danhof; Catherijne A.J. Knibbe

doi:10.1007/s11095-014-1361-z

Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-Physiological Function for Maturation in Glomerular Filtration

Roosmarijn F.W. de Cock
, Karel Allegaert
, Janneke M. Brussee
, Catherine M.T. Sherwin
, Hussain Mulla
, Matthijs de Hoog
, John N. van den Anker
, Meindert Danhof
, Catherijne A.J. Knibbe

Pediatrics

Research output: Contribution to journal › Article › peer-review

Abstract

<p> <h4> PURPOSE: </h4></p><p> Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. <h4> METHODS: </h4></p><p> In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tobramycin and vancomycin collected in 1,760 patients (age 1 day-18 years, bodyweight 415 g-85 kg), a distinction was made between drug-specific and system-specific information. Since the maturational model for clearance is considered to contain system-specific information on the developmental changes in GFR, one GFR maturational function was derived for all three drugs. <h4> RESULTS: </h4></p><p> Simultaneous analysis of these three drugs showed that maturation of GFR mediated clearance from preterm neonates to adults was best described by a bodyweight-dependent exponent (BDE) function with an exponent varying from 1.4 in neonates to 1.0 in adults (ClGFR = Cldrug*(BW/4 kg)(BDE) with BDE = 2.23*BW(-0.065)). Population clearance values (Cldrug) for gentamicin, tobramycin and vancomycin were 0.21, 0.28 and 0.39 L/h for a full term neonate of 4 kg, respectively. <h4> DISCUSSION: </h4></p><p> Based on an integrated analysis of gentamicin, tobramycin and vancomycin, a semi-physiological function for GFR mediated clearance was derived that can potentially be used to establish evidence based dosing regimens of renally excreted drugs in children.</p>

Original language	American English
Pages (from-to)	2643-2654
Journal	Pharmaceutical Research
Volume	31
DOIs	https://doi.org/10.1007/s11095-014-1361-z
State	Published - Oct 1 2014

Keywords

antibiotics
devlopmental changes
glomerular filtration
pediatric age range

Disciplines

Pediatrics

Access to Document

10.1007/s11095-014-1361-z

Cite this

de Cock, R. F. W., Allegaert, K., Brussee, J. M., Sherwin, C. M. T., Mulla, H., Hoog, M. D., van den Anker, J. N., Danhof, M., & Knibbe, C. A. J. (2014). Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-Physiological Function for Maturation in Glomerular Filtration. Pharmaceutical Research, 31, 2643-2654. https://doi.org/10.1007/s11095-014-1361-z

Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-Physiological Function for Maturation in Glomerular Filtration. / de Cock, Roosmarijn F.W.; Allegaert, Karel; Brussee, Janneke M. et al.
In: Pharmaceutical Research, Vol. 31, 01.10.2014, p. 2643-2654.

Research output: Contribution to journal › Article › peer-review

de Cock, RFW, Allegaert, K, Brussee, JM, Sherwin, CMT, Mulla, H, Hoog, MD, van den Anker, JN, Danhof, M & Knibbe, CAJ 2014, 'Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-Physiological Function for Maturation in Glomerular Filtration', Pharmaceutical Research, vol. 31, pp. 2643-2654. https://doi.org/10.1007/s11095-014-1361-z

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title = "Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-Physiological Function for Maturation in Glomerular Filtration",

abstract = " PURPOSE: Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. METHODS: In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tobramycin and vancomycin collected in 1,760 patients (age 1 day-18 years, bodyweight 415 g-85 kg), a distinction was made between drug-specific and system-specific information. Since the maturational model for clearance is considered to contain system-specific information on the developmental changes in GFR, one GFR maturational function was derived for all three drugs. RESULTS: Simultaneous analysis of these three drugs showed that maturation of GFR mediated clearance from preterm neonates to adults was best described by a bodyweight-dependent exponent (BDE) function with an exponent varying from 1.4 in neonates to 1.0 in adults (ClGFR\ =\ Cldrug*(BW/4 kg)(BDE) with BDE\ =\ 2.23*BW(-0.065)). Population clearance values (Cldrug) for gentamicin, tobramycin and vancomycin were 0.21, 0.28 and 0.39 L/h for a full term neonate of 4 kg, respectively. DISCUSSION: Based on an integrated analysis of gentamicin, tobramycin and vancomycin, a semi-physiological function for GFR mediated clearance was derived that can potentially be used to establish evidence based dosing regimens of renally excreted drugs in children.",

keywords = "antibiotics, devlopmental changes, glomerular filtration, pediatric age range",

author = "\{de Cock\}, \{Roosmarijn F.W.\} and Karel Allegaert and Brussee, \{Janneke M.\} and Sherwin, \{Catherine M.T.\} and Hussain Mulla and Hoog, \{Matthijs de\} and \{van den Anker\}, \{John N.\} and Meindert Danhof and Knibbe, \{Catherijne A.J.\}",

year = "2014",

month = oct,

day = "1",

doi = "10.1007/s11095-014-1361-z",

language = "American English",

volume = "31",

pages = "2643--2654",

journal = "Pharmaceutical Research",

}

TY - JOUR

T1 - Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults

T2 - Towards a Semi-Physiological Function for Maturation in Glomerular Filtration

AU - de Cock, Roosmarijn F.W.

AU - Allegaert, Karel

AU - Brussee, Janneke M.

AU - Sherwin, Catherine M.T.

AU - Mulla, Hussain

AU - Hoog, Matthijs de

AU - van den Anker, John N.

AU - Danhof, Meindert

AU - Knibbe, Catherijne A.J.

PY - 2014/10/1

Y1 - 2014/10/1

N2 - PURPOSE: Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. METHODS: In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tobramycin and vancomycin collected in 1,760 patients (age 1 day-18 years, bodyweight 415 g-85 kg), a distinction was made between drug-specific and system-specific information. Since the maturational model for clearance is considered to contain system-specific information on the developmental changes in GFR, one GFR maturational function was derived for all three drugs. RESULTS: Simultaneous analysis of these three drugs showed that maturation of GFR mediated clearance from preterm neonates to adults was best described by a bodyweight-dependent exponent (BDE) function with an exponent varying from 1.4 in neonates to 1.0 in adults (ClGFR = Cldrug*(BW/4 kg)(BDE) with BDE = 2.23*BW(-0.065)). Population clearance values (Cldrug) for gentamicin, tobramycin and vancomycin were 0.21, 0.28 and 0.39 L/h for a full term neonate of 4 kg, respectively. DISCUSSION: Based on an integrated analysis of gentamicin, tobramycin and vancomycin, a semi-physiological function for GFR mediated clearance was derived that can potentially be used to establish evidence based dosing regimens of renally excreted drugs in children.

AB - PURPOSE: Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults. METHODS: In the pharmacokinetic analysis (NONMEM VI) based on data of gentamicin, tobramycin and vancomycin collected in 1,760 patients (age 1 day-18 years, bodyweight 415 g-85 kg), a distinction was made between drug-specific and system-specific information. Since the maturational model for clearance is considered to contain system-specific information on the developmental changes in GFR, one GFR maturational function was derived for all three drugs. RESULTS: Simultaneous analysis of these three drugs showed that maturation of GFR mediated clearance from preterm neonates to adults was best described by a bodyweight-dependent exponent (BDE) function with an exponent varying from 1.4 in neonates to 1.0 in adults (ClGFR = Cldrug*(BW/4 kg)(BDE) with BDE = 2.23*BW(-0.065)). Population clearance values (Cldrug) for gentamicin, tobramycin and vancomycin were 0.21, 0.28 and 0.39 L/h for a full term neonate of 4 kg, respectively. DISCUSSION: Based on an integrated analysis of gentamicin, tobramycin and vancomycin, a semi-physiological function for GFR mediated clearance was derived that can potentially be used to establish evidence based dosing regimens of renally excreted drugs in children.

KW - antibiotics

KW - devlopmental changes

KW - glomerular filtration

KW - pediatric age range

UR - https://corescholar.libraries.wright.edu/pediatrics/350

U2 - 10.1007/s11095-014-1361-z

DO - 10.1007/s11095-014-1361-z

M3 - Article

VL - 31

SP - 2643

EP - 2654

JO - Pharmaceutical Research

JF - Pharmaceutical Research

ER -

Simultaneous Pharmacokinetic Modeling of Gentamicin, Tobramycin and Vancomycin Clearance from Neonates to Adults: Towards a Semi-Physiological Function for Maturation in Glomerular Filtration

Abstract

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