May 29, 2017
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Clinolipid

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Clinolipid

CLINICAL PHARMACOLOGY

CLINOLIPID administered intravenously provides biologically utilizable source of calories and essential fatty acids.

Mechanism Of Action

Fatty acids serve as an important substrate for energy production. The most common mechanism of action for energy production derived from fatty acid metabolism is beta oxidation. Fatty acids are important for membrane structure and function, precursors for bioactive molecules (such as prostaglandins), and as regulators of gene expression.

Pharmacodynamics

Infused essential fatty acids are synthesized into higher derivative fatty acids. Olive oil contains significant amounts of alpha-tocopherol that contributes to Vitamin E status.

Pharmacokinetics

Metabolism And Excretion

The fatty acids, phospholipids, and glycerol found in lipid emulsions are metabolized by cells to carbon dioxide and water. The metabolism of these substances results in the generation of energy in the form of adenosine triphosphate (ATP). Some fatty acids are stored in the body in fat tissue, cell membranes, or as intracellular triglycerides. There is constant turn-over of these tissues, with the result that the lipid components are eventually metabolized to carbon dioxide and water. Carbon dioxide is expired through the lungs. Water is excreted through the kidneys or lost through evaporation/expiration through the skin, lungs, and other tissue surfaces. Some lipids (i.e., phospholipids, cholesterol, and bile acids) are excreted through the biliary system.

Animal Toxicology And/Or Pharmacology

CLINOLIPID was evaluated in toxicity studies conducted in rats and dogs for up to 3 months. The principle signs of toxicity noted in the 3-month studies were:

  • Slight hemolytic anemia at 12 g/kg/day in rats and at 6 g/kg/day in dogs. These doses in rats and dogs are 4.8 and 2.4 times higher, respectively, than the recommended adult dose (2.5 g/kg/day) of CLINOLIPID.
  • Dose-dependent decrease in urea levels in rats at 6 and 12 g/kg/day dose levels and in dogs at 3, 4.5 and 6 g/kg/day dose levels associated with decreased feed consumption.
  • Hypercholesterolemia in dogs at 3, 4.5 and 6 g/kg/day dose levels.
  • Hepatic pathology of lipid and pigmentary overload in male and female rats at 3, 6 and 12 g/kg/day dose levels and brownish-yellow pigmentation in vacuolated Kupffer cells in male and female dogs at 3, 4.5 and 6 g/kg/day dose levels with hepatocyte vacuolation in male dogs at 6 g/kg/day and female dogs at 4.5 and 6 g/kg/day dose levels.
  • Splenic pigmentation and vacuolization in rats at 3, 6 and 12 g/kg/day dose levels, and dogs in 4.5 and 6 g/kg/day dose levels.

At doses of 3 g/kg/day, slight lipid and pigmentary overload of the liver and vacuolization of Kupffer cells were observed in rats and dogs. At a dose of 12 g/kg/day in rats, hepatocellular vacuolation, granulomatous inflammation of the liver, hepatocellular necrosis and hemosiderosis of the liver and lipid deposits and splenic hemosiderosis, were observed. In dogs, at a dose of 6 g/kg/day, brownish-yellow pigmentation in the Kupffer cells of liver and spleen, hyperplasia of vacuolated Kupffer cells, hepatocyte vacuolization, a slight increase in the number of lipid storage cells (Ito cells) in the liver and macrophage vacuolization of the spleen were observed.

Clinical Studies

Two clinical trials (Study 1 and Study 2) in adults compared CLINOLIPID to a pure soybean oil based intravenous lipid emulsion. Although Study 1 and Study 2 were not adequately designed to demonstrate noninferiority of CLINOLIPID to the soybean oil comparator, they support CLINOLIPID injection as a source of calories and essential fatty acids in adults. The lipid dosage was variable in Studies 1 and 2 and adjusted to the patient's nutritional requirements.

Study 1 was a randomized, open-label, multicenter study. Forty eight (48) patients, aged 17 to 75 years, requiring ≥ 15 days (mean 22 days) exclusive parenteral nutrition (TPN) were enrolled and randomized to either CLINOLIPID or a pure soybean oil based intravenous lipid emulsion. Nutritional efficacy was assessed by anthropometric indices (body weight, arm circumference, skin-fold thickness), biomarkers of protein metabolism (total protein, albumin) and lipid metabolism. Anthropometric criteria (body weight, arm circumference, and skin fold thickness) were comparable for both groups. Mean total serum protein and albumin increased similarly in both groups.

Study 2 was a randomized, open label multicenter study that enrolled 22 patients aged 32-81 years who required long-term parenteral nutrition. Twelve patients received CLINOLIPID for a mean of 202 days (range 24 to 408 days) and 10 patients received the comparator lipid for a mean of 145 days (range 29-394 days). The two groups had similar outcomes for weight, weight loss, mid-arm circumference and triceps skinfold thickness.

Last reviewed on RxList: 8/1/2016
This monograph has been modified to include the generic and brand name in many instances.

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