alexa Developmental pharmacokinetics of propylene glycol in preterm and term neonates.
Toxicology

Toxicology

Journal of Clinical Toxicology

Author(s): De Cock RF, Knibbe CA, Kulo A, de Hoon J, Verbesselt R,

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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 (800 mg PG/1000 mg paracetamol) or phenobarbital (700 mg PG/200 mg 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) 630-3980 g, postnatal age (PNA) 1-30 days) using NONMEM 6.2. The model was subsequently used to simulate PG exposure upon administration of paracetamol or phenobarbital in 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) = 0.0849 × {(bBW/2720)(1.69) × (PNA/3)(0.201)}). Volume of distribution scaled allometrically with current bodyweight (V(i) = 0.967 × {(BW/2720)(1.45)}) and was estimated 1.77 times higher when co-administered with phenobarbital compared with 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 range between 33-144 and 28-218 mg l(-1) (peak) and 19-109 and 6-112 mg l(-1) (trough) for paracetamol and phenobarbital formulations, respectively, depending on birth weight and age of the neonates. 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 is dependent on birth weight and PNA. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
This article was published in Br J Clin Pharmacol and referenced in Journal of Clinical Toxicology

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