An Observational Study of Blood Concentrations and Kinetics of Methyl- and Propyl-Parabens in Neonates

H. Mulla; S. Yakkundi; J. McElnay; I. Lutsar; T. Metsvaht; H. Varendi; G. Nellis; A. Nunn; J. Duncan; H. Pandya; M. Turner

doi:10.1007/s11095-014-1520-2

An Observational Study of Blood Concentrations and Kinetics of Methyl- and Propyl-Parabens in Neonates

H. Mulla^*, S. Yakkundi, J. McElnay, I. Lutsar, T. Metsvaht, H. Varendi, G. Nellis, A. Nunn, J. Duncan, H. Pandya, M. Turner

^*Corresponding author for this work

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

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Abstract

Purpose: Systemic exposure to parabens in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients.

Methods: A multi-centre, non-interventional, observational study of excipient-kinetics in neonates. ‘Dried Blood Spot’ samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach.

Results: A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/ml), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CL_{PNA<21 days} 0.57 versus CL_PNA>21days 0.88 L/h.

Conclusions: Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.

Original language	English
Pages (from-to)	1084-1093
Number of pages	10
Journal	Pharmaceutical Research
Volume	32
Issue number	3
Early online date	19 Sept 2014
DOIs	https://doi.org/10.1007/s11095-014-1520-2
Publication status	Published - Mar 2015

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title = "An Observational Study of Blood Concentrations and Kinetics of Methyl- and Propyl-Parabens in Neonates",

abstract = "Purpose: Systemic exposure to parabens in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients.Methods: A multi-centre, non-interventional, observational study of excipient-kinetics in neonates. {\textquoteleft}Dried Blood Spot{\textquoteright} samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach.Results: A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/ml), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CLPNA<21 days 0.57 versus CLPNA>21days 0.88 L/h.Conclusions: Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.",

author = "H. Mulla and S. Yakkundi and J. McElnay and I. Lutsar and T. Metsvaht and H. Varendi and G. Nellis and A. Nunn and J. Duncan and H. Pandya and M. Turner",

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T1 - An Observational Study of Blood Concentrations and Kinetics of Methyl- and Propyl-Parabens in Neonates

AU - Mulla, H.

AU - Yakkundi, S.

AU - McElnay, J.

AU - Lutsar, I.

AU - Metsvaht, T.

AU - Varendi, H.

AU - Nellis, G.

AU - Nunn, A.

AU - Duncan, J.

AU - Pandya, H.

AU - Turner, M.

PY - 2015/3

Y1 - 2015/3

N2 - Purpose: Systemic exposure to parabens in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients.Methods: A multi-centre, non-interventional, observational study of excipient-kinetics in neonates. ‘Dried Blood Spot’ samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach.Results: A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/ml), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CLPNA<21 days 0.57 versus CLPNA>21days 0.88 L/h.Conclusions: Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.

AB - Purpose: Systemic exposure to parabens in the neonatal population, in particular propyl-parabens (PPB), remains a concern. Blood concentrations and kinetics of methyl-parabens (MPB) and PPB were therefore determined in neonates receiving medicines containing these excipients.Methods: A multi-centre, non-interventional, observational study of excipient-kinetics in neonates. ‘Dried Blood Spot’ samples were collected opportunistically at the same time as routine samples and the observations modelled using a non-linear mixed effects approach.Results: A total of 841 blood MPB and PPB concentration data were available for evaluation from 181 pre- and term-neonates. Quantifiable blood concentrations of MPB and PPB were observed in 99% and 49% of patients, and 55% and 25% of all concentrations were above limit of detection (10 ng/ml), respectively. Only MPB data was amenable to modelling. Oral bioavailability was influenced by type of formulation and disposition was best described by a two compartment model with clearance (CL) influenced by post natal age (PNA); CLPNA<21 days 0.57 versus CLPNA>21days 0.88 L/h.Conclusions: Daily repeated administration of parabens containing medicines can result in prolonged systemic exposure to the parent compound in neonates. Animal toxicology studies of PPB that specifically address the neonatal period are required before a permitted daily exposure for this age group can be established.

U2 - 10.1007/s11095-014-1520-2

DO - 10.1007/s11095-014-1520-2

M3 - Article

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VL - 32

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EP - 1093

JO - Pharmaceutical Research

JF - Pharmaceutical Research

IS - 3

ER -

An Observational Study of Blood Concentrations and Kinetics of Methyl- and Propyl-Parabens in Neonates

Abstract

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