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>21 days 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.
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>21 days 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.
Authors: Alan M Hoberman; David K Schreur; Tyra Leazer; George P Daston; Philip Carthew; Thomas Re; Linda Loretz; Peter Mann Journal: Birth Defects Res B Dev Reprod Toxicol Date: 2008-04
Authors: Georgi Nellis; Tuuli Metsvaht; Heili Varendi; Jana Lass; Jennifer Duncan; Anthony J Nunn; Mark A Turner; Irja Lutsar Journal: Paediatr Drugs Date: 2016-06 Impact factor: 3.022
Authors: Luz M Iribarne-Durán; Francisco Artacho-Cordón; Manuela Peña-Caballero; José M Molina-Molina; Inmaculada Jiménez-Díaz; Fernando Vela-Soria; Laura Serrano; José A Hurtado; Mariana F Fernández; Carmen Freire; Nicolás Olea Journal: Environ Health Perspect Date: 2019-11-27 Impact factor: 9.031
Authors: Tyler A Jacobson; Jasdeep S Kler; Yeunook Bae; Jiexi Chen; Daniel T Ladror; Ramsunder Iyer; Denise A Nunes; Nathan D Montgomery; Joachim D Pleil; William E Funk Journal: J Expo Sci Environ Epidemiol Date: 2022-08-13 Impact factor: 6.371
Authors: Lorrene A Buckley; Smita Salunke; Karen Thompson; Gerri Baer; Darren Fegley; Mark A Turner Journal: Int J Pharm Date: 2017-07-17 Impact factor: 5.875