| Therapeutic drug monitoring(TDM) is a novel discipline of therapeutics. It formulates individual plans of treatment to enhance therapeutic effects or decrease adverse effects by motoring drug concentration in body fluids and pharmacokinetics (PK) analysis. TDM is one of the most rapidly progess fields in clinical medicine. The safety, efficiency and rationality of drugs have been improved greatly since TDM was applied. Professor Huang Xi brought forward the hypothesis of traditional Chinese medicine recipe therapeutic drug monitoring (TCMR桾DM), which includes TCM recipe pharmaceutics monitoring, TCM recipe PK monitoring, TCM recipe pharmacodynamics and TCM recipe therapeutics monitoring. If the TCM recipe TDM is carried out, it is possible to clarify the theory of combination and substances of pharmacological effects in TCM recipe and formulate individual plan of treatment with TCM recipe to enhance therapeutic effects or diminish adverse effects. TCM recipe TDM belongs to a new field in TCM recipepharmacology and TCM therapeutics. It is a complex science, so it is impossible for all the four aspects of TCM recipe TDM to progress. This experiment explored the TCM recipe pharmaceutics monitoring and TCM recipe pharmacokinetics monitoring. ObjectiveThis experiment is to monitor the pharmaceutics of Ligusticum Wallichii recipe (LWR) and PK of Ferulic Acid (FA) following LWR decoction in patients with blood stasis and healthy volunteers. Its aim is to explore the TCM recipe pharmaceutics monitoring and TCM recipe clinical PK monitoring of TCMR-TDM. Meanwhile, the results of this experiment can provide further clinical evidence in support of the hypothesis of "syndrome and TCM recipe pharmacokinetics". Method1. Pharmaceutics monitoring of LWR: The quantites of ferulic acid (FA) were detected by HPLC in Ligusticum wallichii decoction (LWD), Ligusticum \vallichi & Radix salviave miltiorrhizae decoction(Z,7?D) and Ligusticum wallichi & Paeonia veitchii Lyunch decoction ( LPD), which were prepared by clinic decoction method.2. Clinical PK monitoring of LWR: (1) The serum samples in healthy volunteers and patients with blood stasis were pretreated with improved boiling water method and the concentration of FA in samples were respectively detected by HPLC. The pharmacokinetic parameters were fitted in 3P97 software respectively, and compare them between two groups. (2) The serum FA concentrations were determined by HPLC in patients with blood stasis following oral administration of LWD, LRD and LPD. The pharmacokinetic parameters were fitted in 3P97 software, and compare theirvariances analysis in SPSS statistics software. Result1. Pharmaceutics monitoring of LWR: (1) Methodological results of HPLC determination of FA concentration in LWR decoction: Methanol-water-acetic acid (36.4:63:0.6, v/v) was used as the mobile phase, while the KromasiL Cjg (150 mm X 4.6 mm, 5 y m) as a fixed phase. FA was detected at the wavelength of 322 nm. Flow rate was l.OmL/min. FA was separated on the baseline under the condition described as above, the linearity in the range of 3.378-7.882ug.mL"' was good (r=0.9971). The intra-assay and inter-assay precisions were less than 5 %; the recovery rates ranged from 94.97+5.4% to 99.25?.2%, and the lowest limit was 0.6756ng. (2) The results of FA determination: the concentrations of FA in LWD, LRD and LPD were 233.16 ?l^ug/g.mL'1, 310.66 ?4.9|ig/g.mL'1 and 178.78 ?5.79jj.g/g.mL" respectively. Compare with LWD group, the concentration of FA in LRD increased distinctly, while the concentration of FA in LPD decreased significantly.2. Clinical PK monitoring of LWR: (1) Methodological results of HPLC determination of FA concentration in serum: Methanol- water- acetic acid (40:59.7:0.3, v/v) was used as the mobile phase, while the Diamonsil(TM) (150 mm X 4.6 mm, 5 u m ) as a fixed phase. FA was detected at the wavelength of 322 nm. Flow rate was l.OmL/min. FA and internal standard were separate... |
PDF Full Text Request