SmofKabiven/SmofKabiven Peripheral Mechanism of Action

Pharmacotherapeutic group: Solutions for parenteral nutrition. ATC code: B05BA10.
Pharmacology: Pharmacodynamics: Lipid emulsion: The lipid emulsion of SmofKabiven/SmofKabiven Peripheral is composed of Smoflipid and has a particle size and biological properties similar to those of endogenous chylomicrons. The constituents of Smoflipid; soya-bean oil, medium-chain triglycerides, olive oil and fish oil have except for their energy contents, their own pharmacodynamic properties.
Soya-bean oil has a high content of essential fatty acids. The omega-6 fatty acid linoleic acid is the most abundant (approx. 55-60%). Alpha-linolenic acid, an omega-3 fatty acid, constitutes about 8%. This part of SmofKabiven/SmofKabiven Peripheral provides the necessary amount of essential fatty acids.
Medium-chain fatty acids are rapidly oxidised and provide the body with a form of immediately available energy.
Olive oil mainly provides energy in the form of mono-unsaturated fatty acids, which are much less prone to peroxidation than the corresponding amount of poly-unsaturated fatty acids.
Fish oil is characterised by a high content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). DHA is an important structural component of cell membranes, whereas EPA is a precursor of eicosanoids as prostaglandines, thromboxanes and leucotrienes.
Two studies providing home parenteral nutrition in patients in need of long-term nutrition support have been performed. The primary objective in both studies was to show safety. Efficacy was the secondary objective in one of the studies, which was done in paediatric patients. This study was stratified by age groups (1 month - <2 years, and 2-11 years respectively). Both studies showed that Smoflipid has the same safety profile as the comparator (Intralipid 20%). Efficacy in the paediatric study was measured by weight gain, height, body mass index, pre-albumin, retinol binding protein and fatty acid profile. There was no difference between the groups in any of the parameters except the fatty acid profile after 4 weeks treatment. The fatty acid profile in the Smoflipid patients revealed an increase in omega-3 fatty acids in plasma lipoproteins and red blood cells phospholipids and hence reflects the composition of the infused lipid emulsion.
Amino acids and electrolytes: The amino acids, constituents of protein in ordinary food, are utilised for tissue protein synthesis and any surplus is channelled to a number of metabolic pathways. Studies have shown a thermogenic effect of amino acid infusion.
Glucose: Glucose should have no pharmacodynamic effects apart from contributing to maintain or replete the normal nutritional status.
Pharmacokinetics: Lipid emulsion: The individual triglycerides in Smoflipid have different clearance rate but Smoflipid as a mixture is eliminated faster than long chain triglycerides (LCT). Olive oil has the slowest clearance rate of the components (somewhat slower than LCT) and medium chain triglycerides (MCT) the fastest. Fish oil in a mixture with LCT has the same clearance rate as LCT alone.
Amino acids and electrolytes: The principal pharmacokinetic properties of the infused amino acids and electrolytes are essentially the same as for amino acids and electrolytes supplied by ordinary food. However, the amino acids of dietary protein first enter the portal vein and then the systemic circulation, while intravenously infused amino acids reach the systemic circulation directly.
Glucose: The pharmacokinetic properties of infused glucose are essentially the same as those of glucose supplied by ordinary food.
Toxicology: Preclinical safety data: Preclinical safety studies with SmofKabiven/SmofKabiven Peripheral have not been performed. However, preclinical data for Smoflipid as well as amino acid and glucose solutions of various concentrations and sodium glycerophosphate reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity and genotoxicity. No teratogenic effects or other embryotoxic injuries could be observed in rabbits with amino acid solutions and are not to be expected from lipid emulsions and sodium glycerophosphate when giving at the recommended doses as substitution therapy. Nutritional products (amino acid solutions, lipid emulsions, and sodium glycerophosphate) used in replacement therapy at physiological levels are not expected to be embryotoxic, teratogenic, or to influence reproductive performance or fertility.
In a test on guinea pigs (maximisation test) fish oil emulsion showed moderate dermal sensitisation. A systemic antigenicity test gave no indication of evidence of anaphylactic potential of fish oil.
In a local tolerance study in rabbits with Smoflipid a slight, transient inflammation after intraarterial, paravenous or subcutaneous administration was observed. After intramuscular administration a moderate transient inflammation and tissue necrosis were seen in some animals.