Biochemical tolerance during low dose propylene glycol exposure in neonates: A formulation-controlled evaluation

Aida Kulo; Anne Smits; Gunnar Naulaers; Jan De Hoon; Karel Allegaert

doi:10.1186/1560-8115-20-5

Biochemical tolerance during low dose propylene glycol exposure in neonates: A formulation-controlled evaluation

Aida Kulo, Anne Smits, Gunnar Naulaers, Jan De Hoon, Karel Allegaert^*

^*Corresponding author for this work

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

11 Citations (Scopus)

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Abstract

Background and purpose of the study:

Propylene glycol (PG) is a frequently co-administered solvent in formulations administered to neonates, but reports on its (in)tolerance are limited. We aimed to report on renal, metabolic and hepatic tolerance before, during and following intravenous (iv) PG-paracetamol exposure and compared these data with similar datasets reported in literature on neonates exposed to PG without paracetamol or paracetamol without PG.

Methods:

Renal (diuresis, creatinemia, sodium), metabolic (Base Excess, Anion Gap, lactate, bicarbonate) and hepatic (liver enzymes, bilirubinemia) indicators before, during and following iv paracetamol-PG exposure in neonates as included in the PARANEO (paracetamol in neonates) study (intra-individual trends, ANOVA) were collected and analysed. Comparison with observations collected in cases exposed to either iv phenobarbital-PG or iv paracetamol-mannitol (inter-individual comparison, Mann Whitney-U test) were made.

Results:

PG exposure (median 34.1 mg/kg/24 h) did not affect postnatal renal, metabolic and hepatic adaptations in 60 cases exposed to paracetamol-PG. These indicators were similar when compared to 29 cases exposed to phenobarbital- PG or 172 cases exposed to paracetamol-mannitol.

Major conclusion:

Based on observations in 89 neonates, low dose PG exposure was tolerated well. Studies on PG pharmacokinetics and its covariates are needed to estimate the upper level of PG tolerance in neonates.

Original language	English
Article number	5
Journal	DARU, Journal of Pharmaceutical Sciences
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/1560-8115-20-5
Publication status	Published - 19 Jul 2012
Externally published	Yes

Bibliographical note

Funding Information:
Aida Kulo was supported by a Join EU-SEE scholarship, Karel Allegaert by the Fund for Scientific Research, Flanders (Fundamental Clinical Investigatorship 1800209 N). This work has been facilitated thanks to the dr Monique Govaerts award 2006–2008 for clinical toxicology, Royal Academia of Medicine, Belgium.

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Biochemical tolerance during low dose propylene glycol exposure in neonatesFinal published version, 262 KBLicence: CC BY

Cite this

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title = "Biochemical tolerance during low dose propylene glycol exposure in neonates: A formulation-controlled evaluation",

abstract = "Background and purpose of the study: Propylene glycol (PG) is a frequently co-administered solvent in formulations administered to neonates, but reports on its (in)tolerance are limited. We aimed to report on renal, metabolic and hepatic tolerance before, during and following intravenous (iv) PG-paracetamol exposure and compared these data with similar datasets reported in literature on neonates exposed to PG without paracetamol or paracetamol without PG. Methods: Renal (diuresis, creatinemia, sodium), metabolic (Base Excess, Anion Gap, lactate, bicarbonate) and hepatic (liver enzymes, bilirubinemia) indicators before, during and following iv paracetamol-PG exposure in neonates as included in the PARANEO (paracetamol in neonates) study (intra-individual trends, ANOVA) were collected and analysed. Comparison with observations collected in cases exposed to either iv phenobarbital-PG or iv paracetamol-mannitol (inter-individual comparison, Mann Whitney-U test) were made. Results: PG exposure (median 34.1 mg/kg/24 h) did not affect postnatal renal, metabolic and hepatic adaptations in 60 cases exposed to paracetamol-PG. These indicators were similar when compared to 29 cases exposed to phenobarbital- PG or 172 cases exposed to paracetamol-mannitol. Major conclusion: Based on observations in 89 neonates, low dose PG exposure was tolerated well. Studies on PG pharmacokinetics and its covariates are needed to estimate the upper level of PG tolerance in neonates.",

author = "Aida Kulo and Anne Smits and Gunnar Naulaers and \{De Hoon\}, Jan and Karel Allegaert",

note = "Funding Information: Aida Kulo was supported by a Join EU-SEE scholarship, Karel Allegaert by the Fund for Scientific Research, Flanders (Fundamental Clinical Investigatorship 1800209 N). This work has been facilitated thanks to the dr Monique Govaerts award 2006–2008 for clinical toxicology, Royal Academia of Medicine, Belgium. ",

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doi = "10.1186/1560-8115-20-5",

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T1 - Biochemical tolerance during low dose propylene glycol exposure in neonates

T2 - A formulation-controlled evaluation

AU - Kulo, Aida

AU - Smits, Anne

AU - Naulaers, Gunnar

AU - De Hoon, Jan

AU - Allegaert, Karel

N1 - Funding Information: Aida Kulo was supported by a Join EU-SEE scholarship, Karel Allegaert by the Fund for Scientific Research, Flanders (Fundamental Clinical Investigatorship 1800209 N). This work has been facilitated thanks to the dr Monique Govaerts award 2006–2008 for clinical toxicology, Royal Academia of Medicine, Belgium.

PY - 2012/7/19

Y1 - 2012/7/19

N2 - Background and purpose of the study: Propylene glycol (PG) is a frequently co-administered solvent in formulations administered to neonates, but reports on its (in)tolerance are limited. We aimed to report on renal, metabolic and hepatic tolerance before, during and following intravenous (iv) PG-paracetamol exposure and compared these data with similar datasets reported in literature on neonates exposed to PG without paracetamol or paracetamol without PG. Methods: Renal (diuresis, creatinemia, sodium), metabolic (Base Excess, Anion Gap, lactate, bicarbonate) and hepatic (liver enzymes, bilirubinemia) indicators before, during and following iv paracetamol-PG exposure in neonates as included in the PARANEO (paracetamol in neonates) study (intra-individual trends, ANOVA) were collected and analysed. Comparison with observations collected in cases exposed to either iv phenobarbital-PG or iv paracetamol-mannitol (inter-individual comparison, Mann Whitney-U test) were made. Results: PG exposure (median 34.1 mg/kg/24 h) did not affect postnatal renal, metabolic and hepatic adaptations in 60 cases exposed to paracetamol-PG. These indicators were similar when compared to 29 cases exposed to phenobarbital- PG or 172 cases exposed to paracetamol-mannitol. Major conclusion: Based on observations in 89 neonates, low dose PG exposure was tolerated well. Studies on PG pharmacokinetics and its covariates are needed to estimate the upper level of PG tolerance in neonates.

AB - Background and purpose of the study: Propylene glycol (PG) is a frequently co-administered solvent in formulations administered to neonates, but reports on its (in)tolerance are limited. We aimed to report on renal, metabolic and hepatic tolerance before, during and following intravenous (iv) PG-paracetamol exposure and compared these data with similar datasets reported in literature on neonates exposed to PG without paracetamol or paracetamol without PG. Methods: Renal (diuresis, creatinemia, sodium), metabolic (Base Excess, Anion Gap, lactate, bicarbonate) and hepatic (liver enzymes, bilirubinemia) indicators before, during and following iv paracetamol-PG exposure in neonates as included in the PARANEO (paracetamol in neonates) study (intra-individual trends, ANOVA) were collected and analysed. Comparison with observations collected in cases exposed to either iv phenobarbital-PG or iv paracetamol-mannitol (inter-individual comparison, Mann Whitney-U test) were made. Results: PG exposure (median 34.1 mg/kg/24 h) did not affect postnatal renal, metabolic and hepatic adaptations in 60 cases exposed to paracetamol-PG. These indicators were similar when compared to 29 cases exposed to phenobarbital- PG or 172 cases exposed to paracetamol-mannitol. Major conclusion: Based on observations in 89 neonates, low dose PG exposure was tolerated well. Studies on PG pharmacokinetics and its covariates are needed to estimate the upper level of PG tolerance in neonates.

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C2 - 23230503

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SN - 1560-8115

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JO - DARU, Journal of Pharmaceutical Sciences

JF - DARU, Journal of Pharmaceutical Sciences

IS - 1

M1 - 5

ER -

Biochemical tolerance during low dose propylene glycol exposure in neonates: A formulation-controlled evaluation

Abstract

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