Open Access The effect of β-cyclodextrin complexation on the bioavailability and hepatotoxicity of clotrimazole

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Abstract:

Clotrimazole, a poorly water-soluble antimycotic agent, is a promising therapeutic agent for various diseases including cancer and sickle cell anemia. The oral bioavailability and hepatic toxicity of clotrimazole were compared with its β-cyclodextrin inclusion form which was prepared by the spray-drying method. The inclusion complex gave significantly higher initial plasma concentrations, Cmax and AUC than did clotrimazole alone, indicating that the drug from the inclusion compound could be more easily absorbed in rats. Furthermore, mice treated with the inclusion compound showed significantly higher GOT/GPT values compared to clotrimazole alone. The inclusion compound also induced hypertrophy of hepatic cells by fat accumulation and disappearance of hepatic sinusoids, indications of pathological changes of liver, suggesting that the inclusion compound could induce more severe tissue damage in the liver than clotrimazole alone. Thus, hepatotoxicity of clotrimazole seems to be correlated with the enhanced oral bioavailability by inclusion complexation. Our results suggest that, in the development of a novel oral product, appearance or enhancement of hepatic toxicity must be considered along with oral bioavailability.

Document Type: Research Article

DOI: http://dx.doi.org/10.1691/ph.2007.10.7018

Affiliations: 1: College of Pharmacy, Yeungnam University, Gyeongsan, South Korea 2: Department of Anatomy, College of Veterinary Medicine, Kyungpook National University, Daegu, South Korea 3: School of Textiles, Yeungnam University, Gyongsan, South Korea 4: College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan, 712-749, South Korea, Email: jakim@yu.ac.kr 5: College of Pharmacy, Yeungnam University, 214-1 Dae-dong, Gyeongsan, 712-749, South Korea, Email: hangon@yu.ac.kr

Publication date: October 1, 2007

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  • Pharmazie is one of the world's leading pharmaceutical journals. As a peer-reviewed scientific journal, DiePharmazie is regularly indexed in Current Contents/Life Sciences, Excerpta Medica, Analytical Abstracts, International Pharmaceutical Abstracts, Beilstein Current Facts in Chemistry, Chemical Engineering and Biotechnology Abstracts (CEABA) and Science Citation Index.
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