Comparison study on the pharmacokinetic and tissue distribution of honokiol and its metabolites between normal and diabetic rats / 药学学报

This study was designed to compare normal and diabetic rats in the pharmacokinetic and tissue distribution of honokiol and its metabolites. Type 2 diabetic rat model was established using high-fat diet feeding for 6 weeks followed by single intraperitoneal injection of low dose (30 mg·kg-1) strepotozotocin. The concentration of honokiol and its metabolites were determined by high performance liquid chromatography. Pharmacokinetic parameters were calculated using DAS 3.0 software. The Cmax of honokiol in the normal rats and diabetic rats are 872.5 ±233.1 and 614.7 ±182.4 μg·L-1 respectively (P -1 respectively. Meanwhile, AUC0-t and Cmax of the metabolite M2 were significantly increased in diabetic rats. The concentrations of honokiol in liver, kidney and brain in the diabetic model group were higher than those of the normal control group. Meanwhile, the exposure of M1 in liver, M2 in liver and kidney of the model group were higher than that in the normal group. The data suggest that the pharmacokinetics and tissue distribution of honokiol and its metabolites are changed in the pathological state of diabetes.

Prediction of ocular irritancy of 26 chemicals and 26 cosmetic products with isolated rabbit eye (IRE) test.

OBJECTIVE: This study aims to establish and evaluate the methodology of isolated rabbit eye (IRE) test. METHODS: IRE test was performed according to modifications of the in vitro toxicology (INVITTOX) Protocol No.85: Rabbit enucleated eye test by European Centre for the Validation of Alternative Methods (ECVAM), and then 26 chemicals and 26 cosmetic products were tested in both in vitro IRE and in vivo Draize tests. A statistical analysis was conducted to determine the relevance of the IRE test to the data generated in the Draize test. RESULTS: IRE test was established successfully in our laboratory. It was shown that ranking correlation and class concordance were fairly well between the IRE test and the Draize test for 26 reference chemicals (Fisher's Exact Test χ(2)=51.314, P<0.001; McNemar P=0.261; Gamma=0.960, P<0.001; Kappa=0.843, P<0.001) and 26 cosmetic products (Fisher's Exact Test χ(2)=15.522, P<0.001; McNemar P=0.311; Gamma=0.967, P<0.001; Kappa=0.611, P<0.001). CONCLUSION: IRE test was established successfully for in vitro testing of eye irritation as an alternative to Draize test.