| Developmental pharmacokinetics of propylene glycol in preterm and term neonates. | |
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MedLine Citation:
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PMID: 22536830 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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Roosmarijn F W De Cock; Catherijne A J Knibbe; Aida Kulo; Jan de Hoon; Rene Verbesselt; Meindert Danhof; Karel Allegaert |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-4-27 |
Journal Detail:
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Title: British journal of clinical pharmacology Volume: - ISSN: 1365-2125 ISO Abbreviation: - Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-4-27 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7503323 Medline TA: Br J Clin Pharmacol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society. |
Affiliation:
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Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands Centre for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia Herzegovina Neonatal Intensive Care Unit, University Hospitals Leuven, Leuven, Belgium. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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