Pharmacokinetics Of Bile Acids In Several Traditional Chinese Medicines And Compound Medicines

OBJIECTIVE: Pharmacokinetics of bile acids in monomer compounds, artificial calculus bovis, natural calculus bovis, qingkailing injection and angongniuhuangwan in biological specimen were studied using a simple, rapid, sensitive and reliable HPLC-MS method. The reasons for difference of pharmacodynamics were analyzed from pharmacokinetics of bile acids in five drugs. It can supply evidence for more optimizing artificial calculus bovis and compatibility of medicines in complex prescription, and search a way to study pharmacyokinetics of traditional Chinese medicines and complex prescription. METHODS: In vivo Drug concentration analytical method and in situ perfused rat intestine model were used. The concentrations of bile acids in mice blood, tissues and perfusate were measured by LC/ESI/MS. RESULTS: 1. The standard curves of bile acids in blood, tissue and perfusate were linear in the range from 4 to 4000 ng? ml^-1 (r>0.999), the lowest limit of quantitation were 4 ng ? ml^-1. The intra- and inter-day precisions were less than 6.0%. 2. Absorption and distributions in heart, lung, kidney and brain of CDCA and DCA were better than CA and HDCA, and absorption and distributions of HDCA were better than CA. 3. There were significant differences (P<0.05) between qingkailing injection group and CA/HDCA group in the main pharmacokinetic parameters and distributions in heart, lung, kidney and brain. Absorption and distribution of CA and HDCA in qingkailing injection group were better than in CA/HDCA group. The concentratons of CA and HDCA in tissues were C_lung> C_kidney>C_henrt>C_? 4. There were significant differences (P<0. 05) among bile acids in monomer compounds, artificial calculus bovis, natural calculus bovis, qingkailing injection and angongniuhuangwan in absorptions and distributions after oral administration. Absorption and distribution of bile acids in angongniuhuangwan were best, qingkailing injection and natural calculus bovis take second place, artificial calculus bovis third and monomer compounds lowest. The results of in situ perfused rat intestine model were similar. 5. There were significant differences (P<0.05) between absorption of bile acids in artificial calculus bovis group and artificial calculus bovis/bilirubin group. AUC of bile acids in artificial calculus bovis/bilirubin group were better than artificial calculus bovis group. CL were lower than in artificial calculus bovis group. Bilirubin could not advance distribution of bile acids in tissues. CONCLUSION: 1. The method is simple, rapid, sensitive and reliable, and it is applicable to assay bile acids in biological samples. 2. Absorption and distribution of CDCA and DCA are better than CA and HDCA, it explains the pharmacological difference with pharmacokinetic results. 3. The parts of non-cholic acid in qingkailing injection can improve absorption and distribution of CA and HDCA. CA and HDCA permeated blood brain barrier uneasily. 4. Absorption and distribution of Monomer compound in mice is lowest, non-bile acids in angongniuhuangwan and qingkailing injection can advance absorption and distribution of bile acids. Other substances(such as bilirubin, inorganic ions, amino acid) in natural calculus bovis can advance absorption and distribution of bile acids. 5. Bilirubin can promote absorption of bile acids in artificial calculus bovis and slow elimination of bile acids. But bilirubin has no effect on distribution of bile acid in artificial calculus bovis, it shows there are other substances contributing to distribution difference between natural and artificial calculus bovis.