The effects on beagles of long-term administration of 20% Travamulsion fat emulsion.

The tolerance of 20% Travamulsion intravenous fat emulsion (Travenol Laboratories, Inc., Deerfield, IL) was studied using male beagle dogs. Physiologic (0.9%) saline, USP, was used as the control, and 10% Travamulsion Intravenous fat emulsion (Travenol Laboratories) as the reference article. The 20 and 10% emulsions were administered intravenously to each of eight animals for 91 days at 20 and 40 ml/kg/day, respectively. These dosages were administered over 4 hr and they correspond to approximately 4 g of lipid as soybean oil per kilogram of body weight. The saline was administered to eight animals at 40 ml/kg/day. On day 92, one-half of the animals in each group were necropsied. The remaining dogs were observed and necropsied on day 122. Toxicity was assessed on animal survival; changes in body weight, urinalysis, and hematologic, and serum biochemical analyses; ophthalmologic examination; gross pathology; and histopathology. The results obtained for the 20% Travamulsion fat emulsion correlated well with those for the 10% Travamulsion fat emulsion. The emulsions were well tolerated and all animals survived and gained weight. The 20% Travamulsion fat emulsion administered provided about 45% of the total caloric requirement of the dog, which is equal to an often used clinical dose. However, caloric administration in the form of lipid emulsion in relation to total energy required was performed at three to six times the indicated clinical rate. In addition to demonstrating that it is safe for prolonged administration, the 20% Travamulsion fat emulsion offers an advantage over the 10% Travamulsion fat emulsion in providing the same amount of calories because it produces lower serum levels of phospholipid, cholesterol, and triglyceride, and the volume of emulsion required is reduced.

The effects of intravenous administration of 10% travamulsion fat emulsion to beagle dogs for 91 consecutive days.

The tolerance of 10% Travamulsion Intravenous Fat Emulsion (Travenol Laboratories, Inc., Deerfield, IL) was studied using beagle dogs. Physiological (0.9%) saline, USP, was used as the control, and Intralipid 10% Fat Emulsion (Vitrum, Sweden) as the reference article. The emulsions were administered intravenously to each of 10 animals for 91 days at a dosage of 40 ml (approximately 4 g)/kg of body weight/day. The saline was administered to 10 animals at 40 ml/kg/day. On day 92, 7 of the 10 animals in each group were necropsied. The remainder were observed and necropsied at approximately day 160. Toxicity was assessed on the basis of animal survival; changes in body weight, hematology, and serum chemistry; gross pathology; and histopathology. The results obtained for the Travenol emulsion correlated well with those for the Vitrum emulsion. The emulsions were well tolerated and they did not produce any major clinical signs of toxicity. All animals survived and gained weight. The Travenol emulsion administered provided about 45% of the total caloric requirement of the dog which is equal to an often used clinical dose. However, the emulsion was infused at six times the indicated clinical rate. Thus, in addition to demonstrating the similarity of Travenol and Vitrum emulsions, the results of this study indicate that the Travenol emulsion is safe for prolonged administration.

Effects of intravenous administration of Travenol 10% lipid emulsion to miniature swine for 28 consecutive days.

The potential toxicity of Travenol 10% lipid emulsion was studied using miniature swine. Physiological (0.9%) saline, USP, was used as the control, and Intralipid 10% fat emulsion as the reference article. The emulsions were administered intravenously at dosages of 40 milliliters (approximately 4 grams of lipid) and 60 milliliters (approximately 6 grams of lipid) per kilogram of body weight per day to eight animals (four males and four females) in each treatment group on each of 28 consecutive days. The saline was administered to eight animals at 60 milliliters per kilogram per day. On day 29, one half of the male and female animals in each group were necropsied. The remaining pigs were observed and necropsied on either day 56 or 57. Toxicity was assessed on the basis of animal survival; changes in body weight, urinalyses, and hematological, and serum biochemical analyses; ophthalmological examination; gross pathology; and histopathology. The results obtained for the Travenol emulsion correlated well with those for the Intralipid emulsion. The emulsions were well tolerated, and they did not produce any major clinical signs of toxicity. All Travenol emulsion-treated animals survived. In addition to demonstrating the similarity of Travenol and Intralipid emulsions, the results of this study indicate that the Travenol emulsion demonstrated an adequate margin of safety for prolonged administration. Travenol emulsion was well tolerated by miniature swine infused at about one and one-half (40 milliliters per kilogram per day) and two (60 milliliters per kilogram per day) times the proposed clinical dose, and at three and two times the anticipated clinical rate, respectively.