Two Approaches for Evaluating the Effects of Galangin on the Activities and mRNA Expression of Seven CYP450.

Galangin is a marker compound of honey and Alpinia officinarum Hance that exhibits great potential for anti-microbial, anti-diabetic, anti-obesity, anti-tumour and anti-inflammatory applications. Galangin is frequently consumed in combination with common clinical drugs. Here, we evaluated the effects of galangin on cytochrome P450 (CYP)-mediated metabolism, using two different approaches, to predict drug⁻drug interactions. Male Sprague Dawley rats were administered galangin daily for 8 weeks. A "cocktail-probes" approach was employed to evaluate the activities of different CYP450 enzymes. Blood samples of seven probe drugs were analysed using liquid chromatography-tandem mass spectrometry in positive and negative electrospray-ionisation modes. Pharmacokinetic parameters were calculated to identify statistical differences. CYP mRNA-expression levels were investigated in real-time quantitative polymerase chain reaction experiments. The galangin-treated group showed significantly decreased AUC0⁻∞ and Cmax values for CYP1A2, and CYP2B3. The galangin-treated group showed significantly increased AUC0⁻∞ and Cmax values for CYP2C13 and CYP3A1. No significant influences were observed in the pharmacokinetic profiles of CYP2C11, CYP2D4 and CYP2E1. The mRNA-expression results were consistent with the pharmacokinetic results. Thus, CYP450 enzyme activities may be altered by long-term galangin administration, suggesting galangin to be a promising candidate molecule for enhancing oral drug bioavailability and chemoprevention and reversing multidrug resistance.

[Optimization of a floating osmotic pump system of ambroxol hydrochloride using central composite design-response surface methodology and its pharmacokinetics in Beagle dogs].

This paper reported that a new type of floating osmotic pump of ambroxol hydrochloride was designed. Third method apparatus (Chinese Pharmacopeia 2010, appendix XD) was employed to simultaneously evaluate the release and floating behavior in vitro. The system was optimized using central composite design-response surface methodology. Similar factor (f2) between the release profile of self-made formulation and the target release profile was chosen as dependent factor. The amount of glucose (A, mg), pore former (B, %) and weight of coating (C, %) were employed as independent factors. Optimized formulation was: A (100.99 mg), B (1.70%), C (4.21%). The value of f2 (89.14) was higher than that of market capsules (69.02) and self-made tablets (72.15). It was showed that self-made capsules possessed character of zero-order release (r = 0.994 4) and drug release completely (>90%). It was showed in result of in vivo study that tmax and Cmax of self-made capsules were significantly lower than that of market capsules and self-made tablets. The correlation coefficient between the fraction of absorption in vivo and the release rate in vitro was 0.985 1, and relative bioequivalence of self-made capsules was 110.77%. Accordingly, self-made capsules displayed obviously characteristics of controlled release both in vivo and in vitro.