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

Allegaert, Karel

doi:10.4172/2161-0495.1000e113

Cited by 7 publications

(10 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many external factors have been proposed to contribute to malfunction of neonatal kidneys, including maternal diet, stress, hypertension, and drugs administered to the mother or to the newborn [46, 47]. Drug formulations, in particular, contain propylene glycol and poly-ethylene glycol, which are co-solvents and could be a factor in the kidney injury [48–50] or a possible environmental contaminant.…”

Section: Discussionmentioning

confidence: 99%

Preterm neonatal urinary renal developmental and acute kidney injury metabolomic profiling: an exploratory study

et al. 2016

View full text Add to dashboard Cite

Introduction AKI staging has been developed in the adult and pediatric populations, but these do not yet exist for the neonatal population. Metabolomics was utilized to uncover biomarkers of normal and AKI associated renal function in preterm infants. The study was comprised of 20 preterm infants with an AKI diagnosis who were matched by gestational age and gender to 20 infants without an AKI diagnosis. Methods Urine samples from pre-term newborn infants collected on day 2 of life were analyzed using broad spectrum NMR-metabolomics. Multivariate analysis methods were used to identify metabolite profiles that differentiated AKI and no AKI, and to identify a metabolomics profile correlating with gestational age in infants with and without AKI. Results There was a clear distinction between the AKI and no-AKI profiles. Two previously identified biomarkers of AKI, hippurate and homovanillate, differentiated AKI and no-AKI. Pathway analysis revealed similarities to cholingeric neurons, prenatal nicotine exposure on pancreatic β cells, and Amitraz-induced inhibition of insulin secretion. Additionally, a pH difference was noted. Both pH and the metabolites were found to be associated of AKI; however, only the metabotype was a significant predictor of AKI. Pathways for the no-AKI group that were uniquely correlated to gestational age included aminoacyl-t-RNA biosynthesis, whereas pathways in the AKI group yielded potential metabolite changes in pyruvate metabolism. Conclusions Metabolomics was able to differentiate the urinary profiles of neonates with and without an AKI diagnosis and metabolic developmental profiles were correlated with gestational age. Further studies in larger cohorts are needed to validate these results.

show abstract

Section: Discussionmentioning

confidence: 99%

Preterm neonatal urinary renal developmental and acute kidney injury metabolomic profiling: an exploratory study

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Exposure to high doses of PG may affect the Central Nervous System, especially in new-borns and children under 4 years of age [ 29 ]. Due to children’s physiological and metabolic immaturity, PG can accumulate rapidly causing toxicity [ 33 ]. In new-borns, its half-life is very long, almost seventeen hours, compared to that of adults, which is about five hours [ 29 ].…”

Section: Excipients: Functions and Main Adverse Effectsmentioning

confidence: 99%

“…In new-borns, its half-life is very long, almost seventeen hours, compared to that of adults, which is about five hours [ 29 ]. The GRAS (Generally Recognized as Safe) classification of excipients typically does not consider the differences in physiological and metabolic maturation between the paediatric and adult populations [ 33 ], a fact that justifies some important adverse reactions presented by PG in the paediatric population [ 29 ]: Hyperosmolar syndrome in burnt children with topical arsenic sulfadiazine ointment containing PG. Precipitation of irreversible deafness in pretermits who received a multivitamin complex containing PG.…”

Section: Excipients: Functions and Main Adverse Effectsmentioning

confidence: 99%

“…In the 1980s, cases of biochemical abnormalities, including hyperosmolarity, lactic acidosis and elevated levels of creatinine and bilirubin, were documented after exposure to 3 g/day of PG and for at least 5 consecutive days. Clinical symptoms, including seizures and bradycardia episodes [ 33 ], then appeared. In 2011, the U.S. FDA reported health problems in premature new-borns associated with the use of Kaletra ® (lopinavir/ritonavir) solution; liquid preparation containing high amounts of PG and ethanol [ 33 , 34 ].…”

Section: Excipients: Functions and Main Adverse Effectsmentioning

confidence: 99%

“…Thus, the study of Allegaert J. [ 33 ] in terms of the PG research project in new-borns is of great interest, as it provides scientific evidence on the tolerance and plasma clearance of this excipient, including differences in elimination pathways (renal pathway compared to the hepatic pathway).…”

Section: Excipients: Functions and Main Adverse Effectsmentioning

confidence: 99%

See 2 more Smart Citations

Excipients in the Paediatric Population: A Review

et al. 2021

View full text Add to dashboard Cite

This theoretical study seeks to critically review the use of excipients in the paediatric population. This study is based on the rules and recommendations of European and American drug regulatory agencies. On the one hand, this review describes the most frequent excipients used in paediatric medicine formulations, identifying the compounds that scientific literature has marked as potentially harmful regarding the side effects generated after exposure. On the other hand, this review also highlights the importance of carrying out safety -checks on the excipients, which, in most cases, are linked to toxicity studies. An excipient in the compilation of paediatric population databases is expected to target safety and toxicity, as in the STEP database. Finally, a promising pharmaceutical form for child population, ODT (Orally Disintegrating Tablets), will be studied.

show abstract

Propylene Glycol Intake From Medications Used on Paediatric Intensive Care

Patel

Langley

Isaac

2014

Archives of Disease in Childhood

View full text Add to dashboard Cite

There is an increasing number of reports of propylene glycol (PG) toxicity in the literature, regardless of its inclusion on the Generally Recognized as Safe List (GRAS).1 PG is an excipient used in many medications as a solvent for water-insoluble drugs. Polypharmacy may increase PG exposure in vulnerable PICU patients who may accumulate PG due to compromised liver and renal function. The study aim was to quantify PG intake in PICU patients and attitudes of clinicians towards PG. Method A snapshot of 50 PICU patients oral or intravenous medication intake was collected. Other data collected included age, weight, diagnosis, lactate levels and renal function. Manufacturers were contacted for PG content and then converted to mg/kg. Excipients in formulations that compete with the PG metabolism pathway were recorded. The Intensivists' opinions on PG intake was sought via e-survey. Results The 50 patients were prescribed 62 drugs and 83 formulations, 43/83 (52%) were parenteral formulations.Median weight of the patients was 5.5 kg (range 2–50 kg), ages ranged from 1 day to 13 years of age.Eleven of the patients were classed as renally impaired (defined as 1.5 times the baseline creatinine).Sixteen formulations contained PG, 2/16 were parenteral, 6/16 unlicensed preparations.Thirty-eight patients received at least one prescription containing PG and 29/38 of these patients were receiving formulations that contained excipients that may have competed with the metabolic pathways of PG.PG intake ranged from 0.002 mg/kg/day to 250 mg/kg/day.Total intake was inconclusive for 2 patients due to a of lack of availability of information from the manufacturer; these formulations were licensed but used in for off-label indications. Five commonly used formulations contributed to higher intakes of PG, namely co-trimoxazole, dexamethasone, potassium chloride, dipyridamole and phenobarbitone.Lactate levels were difficult to interpret due to the underlying conditions of the patients.One of the sixteen intensivist was aware of PG content in drugs, 16/16 would actively change therapy if intake was above European Medicines Agency recommendations. Conclusions Certain formulations used on PICU can considerably increase PG exposure to patients. Due to a lack of awareness of PG content, these should be highlighted to the clinician to assist with making informed decisions regarding risks versus benefits in continuing that drug, route of administration or formulation.

show abstract

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

Cited by 7 publications

References 18 publications

Preterm neonatal urinary renal developmental and acute kidney injury metabolomic profiling: an exploratory study

Preterm neonatal urinary renal developmental and acute kidney injury metabolomic profiling: an exploratory study

Excipients in the Paediatric Population: A Review

Propylene Glycol Intake From Medications Used on Paediatric Intensive Care

Contact Info

Product

Resources

About