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Toxicity of novel solubilizer of paclitaxel, Aceporol 330, in beagle dogs
- Toxicity of novel solubilizer of paclitaxel, Aceporol 330, in beagle dogs
- Kim Y.W.; Chung K.N.; Kang H.S.; Sheen Y.Y.
- Ewha Authors
- SCOPUS Author ID
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- Journal Title
- Biomolecules and Therapeutics
- Biomolecules and Therapeutics vol. 16, no. 1, pp. 61 - 68
- SCIE; SCOPUS
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- In order to develop an improved paclitaxel formulation vehicle, a micelle forming solubilizer, Aceporol 330 was synthesized. It was previously reported that Aceporol 330 provided the linearity of paclitaxel plasma pharmacokinetics. In this study, the single dose toxicity test and 2-week repeated dose toxicity test of Aceporol 330 was performed in beagle dogs after intravenous administration. Single dose and 2-week repeated dose toxicity test of Aceporol 330 showed fever/generalized erythema, severe vomiting, and diarrhea in beagle dogs. However, those toxicities were less severe than those of Cremophor EL. Blood chemistry analysis of 2-week repeatedly treated beagle dogs with Aceporol 330 showed significant elevation of total cholesterol (TCHO) and triglyceride (TG) compared to that of control group. Cremophor EL also significantly increased total cholesterol (TCHO) and triglyceride (TG) as much as Aceporol 330. Results from this study indicated that Aceporol 330 was less toxic than Cremophor EL. Based on the pharmacokinetic advantages and the low toxicity of Aceporol 330 in single dose and 2-week repeated dose toxicity test, Aceporol 330 has a potential for use as a safer solubilizer for paclitaxel than Cremophor EL.
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