Low but inducible contribution of renal elimination to clearance of propylene glycol in preterm and term neonates

Roosmarijn F.W. De Cock, Karel Allegaert, Sophie Vanhaesebrouck, Jan De Hoon, Rene Verbesselt, Meindert Danhof, Catherijne A.J. Knibbe*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

16 Citations (Scopus)

Abstract

BACKGROUND: 

Despite limited information being available on the pharmacokinetics of excipients, propylene glycol (PG) is often used as an excipient in both adults and children. The aim of this study is to characterize the renal and hepatic elimination of PG in preterm and term neonates. 

METHODS: 

The pharmacokinetic analysis of PG was performed in NONMEM 6.2. on the basis of PG concentrations in plasma and/or urine samples for a total of 69 (pre)term neonates (birth weight 630-3980 g, gestational age 24-41 weeks, postnatal age 1-29 days) who received PG coadministered with intravenous paracetamol (5-10 mg/kg per 6 hours), phenobarbital (5 mg·kg·d), or both. To capture the time-dependent trend in the renal excretion of PG, different models based on time after the first dose, urine volume, and creatinine amount in urine were tested. 

RESULTS:

A one-compartment model parameterized in terms of renal clearance, hepatic clearance, and volume of distribution was found to adequately describe the observations in both plasma and urine. After the first dose was administered, the renal elimination of PG was 15% of total clearance, which increased over time to 25% at 24 hours after the first dose of PG. This increase was best described using a hyperbolic function based on time after the first dose. 

CONCLUSIONS:

Renal elimination of PG in (pre)term neonates is low, particularly compared with the reported percentage of 45% in adults, but it may increase with time after the first dose of PG. To study whether this increase is caused by an autoinduced increase in the renal secretion or a reduction of tubular reabsorption of PG, further research is needed.

Original languageEnglish
Pages (from-to)278-287
Number of pages10
JournalTherapeutic Drug Monitoring
Volume36
Issue number3
DOIs
Publication statusPublished - Jun 2014

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