Title: Developmental pharmacokinetics of propylene glycol in preterm and term neonates
Authors: De Cock, Roosmarijn F W
Knibbe, Catherijne A J
Kulo, Aida
de Hoon, Jan
Verbesselt, René
Danhof, Meindert
Allegaert, Karel # ×
Issue Date: Jan-2013
Publisher: Blackwell Scientific Publications
Series Title: British Journal of Clinical Pharmacology vol:75 issue:1 pages:162-171
Article number: 10.1111/j.1365-2125.2012.04312.x
Abstract: Aim: Propylene glycol (PG) is often applied as an excipient in drug formulations. As these formulations may also be used in neonates, the aim of this study was to characterize the pharmacokinetics of propylene glycol, co-administered intravenously with paracetamol (800mgPG/1000mg paracetamol) or phenobarbital (700mgPG/200mg phenobarbital) in preterm and term neonates. Methods: A population pharmacokinetic analysis was performed based on 372 PG plasma concentrations from 62 (pre)term neonates (birth weight (Bbw) 630-3980g, postnatal age (PNA) 1-30days) using NONMEM 6.2. The model was subsequently used to simulate PG exposure upon administration of paracetamol or henobarbitalin neonates (gestational age 24-40 weeks). Results: In a one compartment model, birth weight and PNA were both identified as covariates for PG clearance using an allometric function (CL(i) =0.0849x{(BWb/2720)(1.69) x(PNA/3)(0.201) }). Volume of distribution scaled allometrically with current bodyweight (V(i) =0.967x{(BW/2720)(1.45) }), and was estimated 1.77 times higher when co-administered with henobarbital compared to paracetamol. By introducing these covariates a large part of the interindividual variability on clearance (65%) as well as on volume of distribution (53%) was explained. The final model shows that for commonly used dosing regimens, the population mean PG peak and trough concentrations ranges between 33-144 and 28-218 mg/L (peak) and 19-109 and 6-112 mg/L (trough) depending on birth weight and age of the neonates for paracetamol and henobarbital formulations, respectively. Conclusion: A pharmacokinetic model was developed for PG co-administered with paracetamol or phenobarbital in neonates. As such, large variability in PG exposure may be expected in neonates which are dependent on birth weight and postnatal age. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
ISSN: 0306-5251
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Clinical Pharmacology Centre (-)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science