LIPIDEM 200MG/ML EMULSION FOR INFUSION

Indication

When incorporated as an active ingredient in combination with other active components like fish oils, soya oil, and olive oil as a prescription medication (SMOFLIPID), medium chain triglycerides (MCTs) constitute a therapy indicated for supplying energy, calories, and essential fatty acids to adult patients, as part of a parenteral nutrition regimen, when oral or enteral nutrition is impossible, insufficient, or contraindicated [F126, F127]. However, given the predominant indication of MCTs for acting as a source of calories and essential fatty acids, the use of MCTs alone or as a component part of various unique, individual patient-tailored composite regimen therapies, MCTs are also ultimately indicated for a wide range of health conditions that involve energy deficiency, malnutrition, or disturbances in the ordinary absorption of dietary fats [A33175, F128]. Such conditions can include Crohn's disease, Waldmann disease, weight maintenance in AIDS, cachexia, and various disturbances in patient bile secretion (like cholestasis, disturbances in hepatic-intestinal circulation of bile acids, intestinal dysbacteriosis), or in pancreatic lipase secretion (like pancreatic failure in the course of cystic fibrosis) [A33175, F128].

Mechanism of Action

Absorption of larger long-chain triglycerides (LCT) requires specific processing in the digestive tract, like emulsification with bile [A33175]. This process is aimed at obtaining the maximum surface for digestion (lipolysis with breakage of ester bonds of triglycerides and with the release of monoglycerides, free fatty acids, and glycerol) [A33175]. The process of digestion of fats occurs largely in the duodenum and initial segment of the jejunum [A33175]. Lipases are found in the pancreatic juice and the brush border [A33175]. Once the aforementioned bonds are broken and the fatty acids and monoglycerides are absorbed into an enterocyte, they undergo resynthesis to triglycerides, in the presence of ligase, co-enzyme A, and ATP. Chylomicrons are formed. They get to the lymph and only then can they be transported to blood and destination organs [A33175]. Release of fats from chylomicrons requires the presence of plasmatic lipases, and only then can they be metabolised or stored as a reserve in the fatty tissue [A33175]. Conversely, hydrolysis of medium chain triglycerides (MCTs, which is faster than LCT hydrolysis anyway) does not require bile and lipase [A33175]. Without hydrolysis, they may also be absorbed by the enterocytes and they do not require re-esterification [A33175]. From enterocytes they are directly absorbed into the portal vein and then transported mainly to the liver. Thus, absorption of MCT is faster than that of LCTs [A33175]. Their metabolism is facilitated as well because they are metabolised by the liver almost completely (only when the liver’s metabolic abilities are exceeded the process is taken over by peripheral tissues) with energy release, regardless of the presence of carnitine (which is necessary for the transport of long-chain fatty acids through the mitochondrial membrane) [A33175]. Thanks to this the availability of medium-chain fatty acids for mitochondrial oxidation is better [A33175]. This means that MCT are an easy and quick source of energy [A33175]. However, it should be borne in mind that quantities of MCT exceeding the abilities of the liver are metabolised peripherally in a carnitine-dependent mechanism, which can increase the demand for it [A33175]. On the other hand, it has been observed that on the enterohormonal pathway (an important element of which is a MCT-induced increase of the YY peptide concentration and a decrease in cholecystokinin release) MCT cause a decrease of appetite and consequently a decrease in energy intake [A33175]. They also interfere with the metabolism of the fatty tissue, by hindering the creation of a deposit from long chain acids [A33175]. It has been proven that an MCT-enriched diet modulates metabolism of fats, which is manifested as a decrease in the concentration of triglycerides and cholesterol [A33175]. Moreover, unlike LCT, MCT do not affect the release of cholecystokinin or the emptying of the gallbladder and they do not increase the secretion of pancreatic enzymes [A33175]. They can speed up the intestinal passage by affecting the release of the YY peptide, but only in the distal sections of the intestine [A33175]. Moreover, it has been found that MCT facilitate absorption of calcium [A33175].

Pharmacokinetics

Absorption

The absorption of medium chain triglycerides is considered rapid [A33175, L2895, F126, F127, F128] but that both long-chain triglycerides and medium chain triglycerides share a similar absorption, which is an absorption rate of about 95% - similar to that of other ingested fats [L784].

Distribution

The apparent volumes of distribution have been researched as approximately 4.5 L for medium chain triglycerides and 19 L for medium chain fatty acids in a typical 70-kg subject [A33174].

Metabolism

In capillaries, both medium chain triglycerides (MCTs) and long-chain triglycerides (LCTs) are hydrolysed by lipoprotein lipase to glycerol and free fatty acids, and medium chain fatty acids (MCFAs) and long chain fatty acids (LCFAs), respectively [F126]. MCTs are hydrolysed at a faster rate than LCTs and therefore have a faster elimination rate [F126]. Free MCFAs then readily enter the liver, kidney, heart and other peripheral organs where they are oxidised by β-oxidation and the citric acid cycle to carbon dioxide and water [F126]. Alternatively, via the ketogenesis pathway, the β-oxidation of fatty acids generates the acetyl-CoA that can lead to the formation of ketone bodies like acetoacetate and β-hydroxybutyrate [F126].

Elimination

Clearance

The clearance of medium chain triglycerides in healthy control subjects was measured to be about 1.93 +/- 0.34 mL.kg-1.min-1 [A33179].

Toxicity

The excess use of medium chain triglycerides (MCTs) can lead to increased plasma levels of medium chain dicarboxylic acids, 3-hydroxy fatty acids and ketone bodies [F126]. Hyperketonaemia was observed in repeat-dose toxicity studies with SMOFLIPID [F126]. If excess MCTs are administered, the capacity of extrahepatic tissues to use ketone bodies is saturated and this may be of particular concern in some diabetes patients [F126]. The increased level of ketone bodies aggravates metabolic acidosis and accelerates the breakdown of homeostatic mechanisms [F126].

Active Ingredient/Synonyms

Caprylic/capric triglyceride | Caprylic/capric triglycerides | Coconut oil, fractioned | Fractionated coconut oil | Fractionated triglyceride of coconut oil | MCT | Medium chain triglyceride | Medium-chain glycerides | Triglycerides, medium-chain | Medium-chain triglycerides |