Biochemical tolerance during low dose propylene glycol exposure in neonates: A formulation-controlled evaluation

Abstract

Background and purpose of the studyPropylene 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.MethodsRenal (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.ResultsPG 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.Major conclusionBased 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.

Propylene Glycol in Neonates: Never Prescribed, Frequently Administered, Hardly Evaluated

“…In consecutive reports, we documented that a median PG exposure of 34 mg/kg/day for 48 hours did not affect the normal renal, metabolic and hepatic adaptations in postnatal life [12]. More recently, these findings were confirmed in a formulation controlled approach (paracetamol-PG compared to paracetamol-mannitol formulation tolerance) [14].…”

Preformulation study and influence of DMSO and propylene glycol on the antioxidant action of isocoumarin paepalantine isolated from Paepalanthus bromelioides

“…Propylene glycol is a fre-Q5 quently co-administered solvent in formulations used in preclinical and clinical studies. This solvent is generally nontoxic and noncarcinogenic, and commonly used solvent for oral, intravenous, and topical pharmaceutical agents (Kulo et al, 2012;Fiume et al, 2012;Healing et al, 2015).…”

Oral Liquids

“…Data in chronic use for children are not available and reports about the tolerance in patients of different ages are usually based on IV application. A daily IV dose of about 34 mg/kg bodyweight is reported to be tolerated in neonates in short time use [17]. As long as there are no data available for oral use the amount tolerated in IV application may be an indication for oral consumption as well.…”