{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:23:34Z","timestamp":1784543014558,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,12,14]],"date-time":"2012-12-14T00:00:00Z","timestamp":1355443200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:p><jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold><\/jats:p><jats:p>\u2022\u2003Propylene glycol is commonly used as an excipient in dose forms and is ingested by neonates when administering different drugs.<\/jats:p><jats:p>\u2022\u2003While propylene glycol is generally considered to be safe, toxic effects like bradycardia, lactic acidosis and convulsions have been reported.<\/jats:p><jats:p>\u2022\u2003Information on the pharmacokinetics of propylene glycol in neonates is lacking to provide insight into the possible risk of toxicity.<\/jats:p><jats:p><jats:bold>WHAT THIS STUDY ADDS<\/jats:bold><\/jats:p><jats:p>\u2022\u2003This study describes the pharmacokinetics of propylene glycol in preterm and term neonates co\u2010administered with paracetamol and phenobarbital.<\/jats:p><jats:p>\u2022\u2003A pharmacokinetic model was developed which identified birth weight and postnatal age as important covariates for clearance.<\/jats:p><jats:p>\u2022\u2003The model was used to simulate exposure to propylene glycol co\u2010administered with both drugs.<\/jats:p><jats:p><jats:bold>AIM<\/jats:bold> 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\u2010administered intravenously with paracetamol (800\u2003mg PG\/1000\u2003mg paracetamol) or phenobarbital (700\u2003mg PG\/200\u2003mg phenobarbital) in preterm and term neonates.<\/jats:p><jats:p><jats:bold>METHODS<\/jats:bold> A population pharmacokinetic analysis was performed based on 372\u2003PG plasma concentrations from 62 (pre)term neonates (birth weight (bBW) 630\u20133980\u2003g, postnatal age (PNA) 1\u201330 days) using NONMEM 6.2. The model was subsequently used to simulate PG exposure upon administration of paracetamol or phenobarbital in neonates (gestational age 24\u201340 weeks).<\/jats:p><jats:p><jats:bold>RESULTS<\/jats:bold> In a one compartment model, birth weight and PNA were both identified as covariates for PG clearance using an allometric function (CL<jats:sub>i<\/jats:sub>= 0.0849 \u00d7 {(bBW\/2720)<jats:sup>1.69<\/jats:sup>\u00d7 (PNA\/3)<jats:sup>0.201<\/jats:sup>}). Volume of distribution scaled allometrically with current bodyweight (<jats:italic>V<\/jats:italic><jats:sub>i<\/jats:sub>= 0.967 \u00d7 {(BW\/2720)<jats:sup>1.45<\/jats:sup>}) and was estimated 1.77 times higher when co\u2010administered with phenobarbital compared with 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 range between 33\u2013144 and 28\u2013218\u2003mg\u2003l<jats:sup>\u22121<\/jats:sup> (peak) and 19\u2013109 and 6\u2013112\u2003mg\u2003l<jats:sup>\u22121<\/jats:sup> (trough) for paracetamol and phenobarbital formulations, respectively, depending on birth weight and age of the neonates.<\/jats:p><jats:p><jats:bold>CONCLUSION<\/jats:bold> A pharmacokinetic model was developed for PG co\u2010administered with paracetamol or phenobarbital in neonates. As such, large variability in PG exposure may be expected in neonates which is dependent on birth weight and PNA.<\/jats:p>","DOI":"10.1111\/j.1365-2125.2012.04312.x","type":"journal-article","created":{"date-parts":[[2012,4,27]],"date-time":"2012-04-27T08:37:42Z","timestamp":1335515862000},"page":"162-171","source":"Crossref","is-referenced-by-count":37,"title":["Developmental pharmacokinetics of propylene glycol in preterm and term neonates"],"prefix":"10.1111","volume":"75","author":[{"given":"Roosmarijn F. W.","family":"De Cock","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherijne A. J.","family":"Knibbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aida","family":"Kulo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"de Hoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Verbesselt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meindert","family":"Danhof","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Allegaert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,12,14]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2010.190330"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-139X.2007.00280.x"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1097\/PCC.0b013e31819a383c"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1542\/peds.99.2.268"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-198709000-00001"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.128.3.1674"},{"key":"e_1_2_7_8_2","unstructured":"CBG\u2010MEB.Medicinal products: allergy information. Accessed September 9 2011."},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/jps.2600740815"},{"key":"e_1_2_7_10_2","doi-asserted-by":"crossref","first-page":"1606","DOI":"10.1001\/jama.1985.03350350100031","article-title":"Hyperosmolality induced by propylene glycol. A complication of silver sulfadiazine therapy","volume":"253","author":"Fligner CL","year":"1985","journal-title":"JAMA"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2009.160192"},{"key":"e_1_2_7_12_2","unstructured":"European Medicines Agency (EMA).Guidelines medicinal products for human use; safety environment and information. Accessed September 9 2011."},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00003246-200212000-00021"},{"key":"e_1_2_7_14_2","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1542\/peds.72.3.353","article-title":"Hyperosmolality in small infants due to propylene glycol","volume":"72","author":"Glasgow AM","year":"1983","journal-title":"Pediatrics"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1177\/0148607187011002169"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2008.146035"},{"key":"e_1_2_7_17_2","unstructured":"Food and Drug Administration.Drug safety communication: serious health problems seen in premature babies given Kaletra (lopinavir\/ritonavir) oral solution. Accessed September 9 2011."},{"key":"e_1_2_7_18_2","unstructured":"BoxwellD CaoK LewisL MarcusK NikharB.Kaletra oral solution toxicity in neonates \u2013 lopinavir ethanol and\/or propylene glycol?18th Conference on Retroviruses and Opportunistic Infections (2011) 2011."},{"key":"e_1_2_7_19_2","volume-title":"Neonatal and Pediatric Pharmacology: Therapeutic Principles in Practice","author":"Yaffe SJ","year":"2010"},{"key":"e_1_2_7_20_2","first-page":"1054","article-title":"Determination of propylene glycol in low volume plasma and urine samples of neonates by LC with photodiode array detection","volume":"95","author":"Kulo A","year":"2011","journal-title":"Chromatographia"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-010-0333-1"},{"key":"e_1_2_7_22_2","first-page":"301","volume-title":"Introduction to Linear Regression Analysis","author":"Montgomery DC","year":"1982"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100241"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2007.12.002"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-006-9067-5"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1592\/phco.28.8.984"},{"key":"e_1_2_7_27_2","first-page":"73","article-title":"Serum and urine osmolality in normal full\u2010term infants","volume":"101","author":"Feldman W","year":"1969","journal-title":"Can Med Assoc J"},{"key":"e_1_2_7_28_2","first-page":"712","article-title":"Measured vs calculated plasma osmolality in infants with very low birth weights","volume":"146","author":"Giacoia GP","year":"1992","journal-title":"Am J Dis Child"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.2165\/11595640-000000000-00000"}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2125.2012.04312.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2125.2012.04312.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T17:56:00Z","timestamp":1697392560000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2125.2012.04312.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,14]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["10.1111\/j.1365-2125.2012.04312.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2125.2012.04312.x","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,14]]}}}