Gillian L Fell1, Bennet S Cho1, Amy Pan1, Vania Nose2, Lorenzo Anez-Bustillos1, Duy T Dao1, Meredith A Baker1, Prathima Nandivada3, Kathleen M Gura4, Mark Puder1. 1. 1 Vascular Biology Program and Department of Surgery, Boston Children's Hospital, Boston, Massachusetts, USA. 2. 2 Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA. 3. 3 Department of Surgery, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA. 4. 4 Department of Pharmacy, Boston Children's Hospital, Boston, Massachusetts, USA.
Abstract
BACKGROUND: Fat emulsions are important components of parenteral nutrition (PN). Fish oil (FO) emulsions reverse cholestasis in PN-associated liver disease. There are 2 FO monographs. One is "FO; rich in omega-3 fatty acids" (NFO). The other, "omega-3 acids," (PFO), is enriched in omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The purpose of this study is to compare the effects of 20% NFO and PFO emulsions produced in the laboratory in a murine model. METHODS: Emulsions were compounded containing different oils: soybean oil (SO), NFO, and two PFOs differing in percentage of fatty acids as triglycerides (PFO66 and PFO90). Chow-fed mice received saline, one of the above emulsions, or a commercial FO (OM) intravenously (2.4 g/kg/day) for 19 days. On day 19, animals were euthanized. Livers, spleens, and lungs were procured for histologic analysis. RESULTS: OM, SO, NFO, and PFO90 were well-tolerated clinically. PFO66 resulted in tachypnea and lethargy for ~1 minute following injections. At euthanasia, PFO66 and PFO90 groups had organomegaly. Histologically, these groups had splenic and hepatic fat-laden macrophages, and lungs had scattered fat deposits. Other groups had normal organs. CONCLUSIONS: PFO emulsions present an attractive possibility for improving inflammation in PN-dependent patients by concentrating anti-inflammatory EPA and DHA. However, 20% PFO emulsions were poorly tolerated and precipitated adverse end organ sequelae, suggesting that they may not be safe. Development of novel manufacturing methods may achieve safe 20% PFO parenteral emulsions, but by established formulation methods, these emulsions were clinically suboptimal despite meeting pharmacopeial standards.
BACKGROUND: Fat emulsions are important components of parenteral nutrition (PN). Fish oil (FO) emulsions reverse cholestasis in PN-associated liver disease. There are 2 FO monographs. One is "FO; rich inomega-3 fatty acids" (NFO). The other, "omega-3 acids," (PFO), is enriched in omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The purpose of this study is to compare the effects of 20% NFO and PFO emulsions produced in the laboratory in a murine model. METHODS: Emulsions were compounded containing different oils: soybeanoil (SO), NFO, and two PFOs differing in percentage of fatty acids as triglycerides (PFO66 and PFO90). Chow-fed mice received saline, one of the above emulsions, or a commercial FO (OM) intravenously (2.4 g/kg/day) for 19 days. On day 19, animals were euthanized. Livers, spleens, and lungs were procured for histologic analysis. RESULTS: OM, SO, NFO, and PFO90 were well-tolerated clinically. PFO66 resulted in tachypnea and lethargy for ~1 minute following injections. At euthanasia, PFO66 and PFO90 groups had organomegaly. Histologically, these groups had splenic and hepatic fat-laden macrophages, and lungs had scattered fat deposits. Other groups had normal organs. CONCLUSIONS:PFO emulsions present an attractive possibility for improving inflammation in PN-dependent patients by concentrating anti-inflammatory EPA and DHA. However, 20% PFO emulsions were poorly tolerated and precipitated adverse end organ sequelae, suggesting that they may not be safe. Development of novel manufacturing methods may achieve safe 20% PFO parenteral emulsions, but by established formulation methods, these emulsions were clinically suboptimal despite meeting pharmacopeial standards.
Authors: Vincent E de Meijer; Kathleen M Gura; Hau D Le; Jonathan A Meisel; Mark Puder Journal: JPEN J Parenter Enteral Nutr Date: 2009-07-01 Impact factor: 4.016
Authors: David F Driscoll; Anthony P Silvestri; Bruce R Bistrian; Bernard A Mikrut Journal: Am J Health Syst Pharm Date: 2007-02-15 Impact factor: 2.637
Authors: Pei-Ra Ling; Charlotte Andersson; Robert Strijbosch; Sang Lee; Anthony Silvestri; Kathleen M Gura; Mark Puder; Bruce R Bistrian Journal: Metabolism Date: 2010-01-25 Impact factor: 8.694
Authors: Karim C El Kasmi; Aimee L Anderson; Michael W Devereaux; Padade M Vue; Wujuan Zhang; Kenneth D R Setchell; Saul J Karpen; Ronald J Sokol Journal: Sci Transl Med Date: 2013-10-09 Impact factor: 17.956
Authors: Beth A Carter; Olga A Taylor; Daniel R Prendergast; Tracy L Zimmerman; Richard Von Furstenberg; David D Moore; Saul J Karpen Journal: Pediatr Res Date: 2007-09 Impact factor: 3.756
Authors: Meredith A Baker; Bennet S Cho; Lorenzo Anez-Bustillos; Duy T Dao; Amy Pan; Alison A O'Loughlin; Zachary M Lans; Paul D Mitchell; Vania Nosé; Kathleen M Gura; Mark Puder; Gillian L Fell Journal: Am J Clin Nutr Date: 2019-04-01 Impact factor: 7.045
Authors: Gillian L Fell; Lorenzo Anez-Bustillos; Duy T Dao; Meredith A Baker; Prathima Nandivada; Bennet S Cho; Amy Pan; Alison A O'Loughlin; Vania Nose; Kathleen M Gura; Mark Puder Journal: PLoS One Date: 2019-07-11 Impact factor: 3.240