A population pharmacokinetic model of vancomycin for dose individualization based on serum cystatin C as a marker of renal function.

OBJECTIVES: This study aimed to establish a vancomycin population pharmacokinetics (PPK) model based on serum cystatin C and to optimize dosing for achieving targeted steady-state trough concentrations (Css ) of 10-15 and 15-20 mg/l. METHODS: Patients aged ≥18 years were prospectively enrolled. A vancomycin PPK model was built with glomerular filtration rate (GFR) as a renal covariate estimated by cystatin C. A new group of patients were used for external evaluation. PPK analysis and Monte Carlo simulations were performed using nonlinear mixed effect modelling programme. KEY FINDINGS: Two hundreds of patients with 514 samples were included. The final model was CL (L/h) = (5.07 × (GFR/105.5)0.524 × (AGE/48.5)-0.309 × (WT/60)0.491 ); V (l) = 46.3. Internal and external evaluations demonstrated good stability and predictability. The average probability of target attainment (PTA) of optimal dosing regimens for targeted Css achieving 10-15 and 15-20 mg/l were 51.2% and 40.6%, respectively. An average PTA ≥71% for targeted concentration of 10-20 mg/l was obtained. CONCLUSIONS: A vancomycin PPK model with cystatin C as the renal marker has good stability and predictability. The new proposed dosing regimens were predicted to achieve a good PTA.

[Study on quality standard of Mucuna pruriens var. utilis].

OBJECTIVE: To provide scientific basis for the utilization and development of Mucuna pruriens var. utilis by establishing its quality control standard. METHODS: The bioactive constituents were analyzed by TLC and HPLC. Moisture, ash and the extracts of Mucuna pruriens var. utilis were all determined. RESULTS: The TLC spots of levodopa had similar color with the control group at the same position. The results of HPLC quantitative analysis showed that the linear range of levodopa was 26.45 to approximately 132.25 microg/mL, r = 0.9992, and the average recovery rate was 103.8%, RSD = 1.85%. CONCLUSIONS: This method is convenient, accurate, reliable with good reproducibility, so it can be used to establish quality standard for the medicinal material.

[Effect of cedemex on cAMP and cGMP levels of different brain areas in morphine withdrawal rats].

OBJECTIVE: To investigate the effect of Cedemex on cAMP and cGMP contents in different brain regions in morphine withdrawal rats precipitated by naloxone. METHOD: A physical morphine dependent model of rats was established by subcutaneous injection of morphine in gradually increasing dosage within 7 days. cAMP and cGMP contents of VTA, cortex and hippocampus of the rat brains were determined by radioimmunoassay. RESULT: The morphine withdrawal symptoms of rats were relieved significantly by ig Cedemex. Compared with the controls, cAMP content in the region of VTA, cortex and hippocampus of the morphine dependent rats were significantly higher (P < 0.05), while cGMP contents in those regions were significantly lower (P < 0.05). cAMP contents in the area of VTA, cortex and hippocampus of the morphine dependent rats were significantly reduced, while cGMP contents were significantly increased by ig Cedemex. CONCLUSION: Cedemex may significantly attenuate the morphine withdrawal symptoms in rats. The mechanism of this effect may be related to adjusting the contents of cAMP and cGMP in some brain regions.

[The inhibitory effect of compound liuyuexue on DHBV DNA].

OBJECTIVE: To study the inhibitory effect of traditional Chinese medicine Compound Liuyuxeue(CLYX) on duck hepatitis B virus (DHBV) DNA, and provide experimental basis for developing a new drug for the clinical treatment. METHODS: One - day old Guangxi brown spotted ducks infected with DHBV were used as the hepatitis B virus infected animal model. Positive ducks were detected by PCR at 13 days after the infection of DHBV, and were randomly divided into five groups: the high dose group, middle dose group and low dose group of Compound Liuyexue( CLYX) , model group, positive control group. Every group had 10 ducks and CLYX was given for 14 days. The content of DHBV DNA in serum were measured by Fluoresceence Quantitative PCR( FQ-PCR). RESULTS: The serum DHBV DNA content was decreased significantly by the treatment with CLYX. The high dose group and middle dose group of CLYX could significantly inhibit DHBV DNA replication in vivo( P <0. 01). DHBV DNA content in serum in high dose group and middle dose group did not return significantly 3 days after stopping treatment, and its inhibitory effects were dose-and tim-dependents. CONCLUSION: CLYX can inhibit significantly DHBV DNA.

[Impact of preoperative lymphatic chemotherapy on relapse and metastasis of breast cancer and its mechanism].

BACKGROUND & OBJECTIVE: Although it is reported that lymphatic chemotherapy could raise drug concentrations in local lymph nodes and prolong survival time of patients with gastrointestinal tumors, its effect on breast cancer has not been explored. This study was to explore the impact of lymphatic chemotherapy on relapse and metastasis of breast cancer, and to investigate the mechanism. METHODS: Sixty patients with breast cancer of stage II-III were randomized into 2 groups: 40 patients in Epi-CH (carbon activated absorbing epirubicin) group were injected with 10 mg of Epi-CH in the tissue around primary tumor 72 h before modified radical resection; 20 patients in control group were injected with 10 mg of aqueous epirubicin in the same region. The stained nodes full of tumor cells in Epi-CH group and non-stained nodes in control group were selected. The apoptotic index (AI) of cancer cells in metastatic axillary lymph node was calculated by TUNEL method; the expression of Fas/Fas-L proteins was examined by SP immunohistochemistry; the relapse and metastatic rate was compared. RESULTS: The AI of cancer cells in metastatic axillary lymph node was significantly higher in Epi-CH group than in control group [(9.5+/-2.7)% vs. (3.8+/-1.4)%, P<0.01]. The expression of Fas protein was significantly higher in Epi-CH group than in control group (P<0.05), but the expression of Fas-L protein had no difference between the 2 groups (P>0.05). No chemotherapy-related local and whole body reaction occurred in both groups. The relapse and metastatic rate was significantly lower in Epi-CH group than in control group (P<0.05). CONCLUSION: Preoperative Epi-CH lymphatic chemotherapy could suppress relapse and metastasis of breast cancer, which might through up-regulating expression of Fas protein and inducing apoptosis of axillary metastasis cells.