The Experimental Study Using Beagle Dogs for the Clinical Application of Poloxamer-solutol Propofol

Ahn, Hyun Hee; Choi, Sang Ho; Lee, Soo Kyung; Kim, Young Mi; Song, Hee Jong; Moon, Hyun Soo; Kil, Ho Yeong

Abstract

BACKGROUND: To reduce side effects such as hyperlipidemia, pain on injection, and bacterial growth of the present formation of propofol, many attempts to change its formulation have been tried. We have developed a newly formulated poloxamer-solutol propofol, which is includes soy bean oil and egg phosphatide as sufactants. The aim of this study was to evaluate the poloxamer-solutol propofol regarding its pharmacokinetic and pharmacodynamic characteristics and bacterial growth compared to original propofol.
METHODS
Thirty Beagle dogs weighing around 10-15 kg were randomly assigned to one of two groups. Group 1 received Diprivan propofol 1% (AstraZeneca Co. UK), Group 2 received poloxamer-solutol formulated propofol by continuous intravenous infusion at 35 mg/kg/h for 3 hours. Three, 6, 9 and 12 hours after the discontinuation of the propofol infusion, venous samples from the anterior tibial vein were analysed for liver and renal function test. Also, blood lipid levels were checked after 3 hours of infusion and blood propofol concentrations were checked every hour during infusion. Eye opening time and orientation time, represented by walking on four legs, were evaluated. Also, broth cultures (100microliter) of four standard preservative efficacy test organisms (Staphylococcus Aureus, Pseudomonas Aeruginosa, Escherichia Coli, Candida Albicans) were added to 9.9 ml of four test formulations at approximately 200 colony forming units/ml. The subjected formulations were; original propofol (AstraZeneca Co, 1% solution, UK), EDTA added propofol (0.0055% EDTA added propofol), Poloxamer-Solutol formulated propofol (poloxamer 188/407 and solutol mixture), and normal saline. The test formulations were incubated at 25degrees C and 32.5degrees C (Tryptic soy agar medium for bacteria and Sabrouraud dextrose agar medium for fungus) and tested for viable counts after 24 and 48 hours.
RESULTS
Poloxamer-solutol propofol showed no increase of triglyceride and the propofol concentrations showed no difference between the two groups. Also the original propofol supported the growth of all microorganisms at both temperatures and times. EDTA added propofol inhibited the growth of microorganisms more than the original propofol, but not as much as the poloxamer-solutol formulated propofol. Saline showed a similar pattern as the propofol with added EDTA.
CONCLUSIONS
The poloxamer-solutol formulated propofol has advantages by pharmacokinetic-pharmacodynamic studies in terms of the initial TG level during propofol infusion, and shows more bacteriostatic activity against all four microorganisms than the original propofol and the propofol with added EDTA.