title: Biochemical tolerance during low dose propylene glycol exposure in neonates: A formulation-controlled evaluation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium ; Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Sarajevo, Sarajevo, Bosnia Herzegovina.
authors.forename: Aida
authors.initials: A
authors.lastname: Kulo
authors.forename: Anne
authors.initials: A
authors.lastname: Smits
authors.forename: Gunnar
authors.initials: G
authors.lastname: Naulaers
authors.forename: Jan
authors.initials: J
authors.lastname: de Hoon
authors.forename: Karel
authors.initials: K
authors.lastname: Allegaert