Intravenous anesthesia


Anesthesia and Pain Medicine. 2004 June 8(2): 101-113
ⓒ Korean Society for Intravenous Anesthesia
Acute Toxicity and Anesthetic Effects of Nano-Particle Formulation of Propofol in Animals
Sung Moon Jeong, M.D., Ji Yong Lee, M.D., and Gyu Jeong Noh, M.D.
Department of Anesthesiololgy and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Background: Aquafol (Daewon Pharm. Co., Ltd., Korea), a new commercial preparation of propofol, is a nano-particle formulation of propofol. The acute toxicity and anesthetic effects of Aquafol was investigated and compared with Diprivan (AstraZeneca, U.K.) in animals.
Methods: Intravenous single dose toxicity (30, 35, 40, 45, and 50 mug/kg of Aquafol ) and dose-escalating toxicity (20, 30, 40 mug/kg of Aquafol ) studies were performed in mice and beagle dogs, respectively. In the control groups of both studies, the same volumes of normal saline were injected instead of Aquafol . The clinical signs, mortality, changes of body weight, necropsy and histopathologic findings were evaluated. The anesthetic effects of single intravenous dose of Aquafol was evaluated in mice, rats, and beagle dogs, in which the doses of Aquafol were 6, 12 and 24 mug/kg in mice and rats, and 3 and 6 mug/kg in beagle dogs. The effects on the spontaneous motor activity and pentobarbital sleeping time in mice, on the respiratory rate and tidal volume in rats, and on the mean arterial pressure (MAP) and heart rate, body temperature and activity in beagle dogs were compared among control, Aquafol , and Diprivan groups.
Results: The approximate lethal dose of Aquafol was 30 45 mug/kg in mice, and 20 25 mug/kg in beagle dogs. The blood concentration of propofol in beagle dogs just before death was 40.7 13.4 mug/ml, showing large inter-individual variability. The cause of death seemed to be congestive heart failure due to overdose of Aquafol . Although Aquafol reduced MAP more than Diprivan , the other anesthetic effects observed in this study were not different from those of Diprivan. Conclusions: The acute toxicity and anesthetic effects of Aquafol were similar to Diprivan.
Key words : Acute toxicity, anesthetic effects, nanoparticle dispersion, propofol
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