Laboratory of Clinical Pharmacology

Lausanne, Switzerland

Laboratory of Clinical Pharmacology

Lausanne, Switzerland
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Fan H.-W.,Nanjing Medical University | Fan H.-W.,Laboratory of Clinical Pharmacology | Sun M.,Anhui University | Li Y.-B.,Nanjing Medical University | And 4 more authors.
Chinese Pharmaceutical Journal | Year: 2010

OBJECTIVE: To investigate the effects of nimodipine on the teniposide concentration in glioma cells and in the tumor-bearing rats, as well as teniposide pharmacodynamics. METHODS: The IC50 of teniposide and the safe concentration of nimodipine were determined by WST-1 method. Under the concentration, the synergistic effect of the drug combination was evaluated. The glioma cells and tumor-bearing rats were divided into two groups treated with teniposide and teniposide with nimodipine, respectively. Cell membrane swelling method was used to get the intracellular fluid of glioma cells. Then, the concentration of teniposide inside the glioma was detected by HPLC-MS/MS method. And the concentrations in glioma tumor-bearing rat plasma and brain tissue were determined in the same way. RESULTS: The concentration of teniposide combined with nimodipine in glioma was as 10 times as that of group treated with teniposide alone at 48 h after the treatment. The plasma concentration of tumor-bearing rats in the group treated with nimodipine and teniposide was 155.02 μg·L-1 while the concentration in group treated with teniposide was 72.25 μg·L-1. The concentrations in normal brain tissue were different. CONCLUSION: Nimodipine can markedly increase the teniposide concentration in glioma cells and in the plasma of tumor-bearing rat, improve the anti-tumor effects. This study provided an evidence for clinical drug combination for glioma patients.


Yang R.,Shenyang Pharmaceutical University | Yang R.,Laboratory of Clinical Pharmacology | Mao Y.,Shenyang Pharmaceutical University | Ye T.,Shenyang Pharmaceutical University | And 2 more authors.
Drug Delivery | Year: 2016

In this study, paclitaxel (PTX)-loaded polyamidoamin-alkali blue (PTX-P-AB) was prepared in order to investigate the intralymphatic targeting ability and anti-cancer effect after subcutaneous (s.c.) administration. The physicochemical properties and in vitro drug release were evaluated. The lymphatic drainage and lymph nodes (LNs) uptake were examined by pharmacokinetics and distribution recovery of PTX in plasma, LNs, injection site (IS) and tissues after s.c. injection in healthy mice and in tumor-bearing mice. The osmotic pressure of PTX-P-AB affecting the lymphatic targeting was studied. The anti-tumor activity of PTX-P-AB was investigated in mice bearing S180 metastatic tumors. Results showed that PTX-P-AB with suitable and stable physicochemical properties could be used for in vivo lymphatic studies, and displayed the more rapid lymphatic absorption, the higher AUC value in LNs, the longer LNs residence time and the higher metastasis-inhibiting rate compared with Taxol®. Enhanced lymphatic drainage from the IS and uptake into lymph by increasing the osmotic pressure of PTX-P-AB indicated that PTX-P-AB possesses the double function of lymphatic tracing and lymphatic targeting, and suggested the potential for the development of lymphatic targeting vectors and the lymphatic tracer for treatment and diagnosis. © 2015 Informa Healthcare USA, Inc.


Xia S.,Laboratory of Clinical Pharmacology | Li L.,Shenyang Pharmaceutical University | Li F.,Shenyang Pharmaceutical University | Peng Y.,Shenyang Pharmaceutical University | And 3 more authors.
Acta Chimica Sinica | Year: 2011

Daphnane-type diterpenes showed potent anti-tumour activities, the flower buds of Daphne genkwa which was rich in daphnane-type diterpenes were subject to phytochemical investigation resulting in the isolation of two novel diterpenes (1, 2) and a known diterpene 3, they were elucidated as 12-O-(2′E,4′E-decadienoyl)-4-hydroxyphorbol-13-acetyl (1), isoyuanhuadine (2) and yuanhuadine (3) by spectroscopic data, including 1H NMR, 13C NMR, HSQC, HMBC, NOESY, ESI-MS and HR-ESI-MS. The new compound isoyanhuadine is yuanhuadine's cis-isomer.


Vogne C.,University of Lausanne | Prod'hom G.,University of Lausanne | Jaton K.,University of Lausanne | Decosterd L.A.,Laboratory of Clinical Pharmacology | Greub G.,University of Lausanne
Clinical Microbiology and Infection | Year: 2014

Carbapenemases should be accurately and rapidly detected, given their possible epidemiological spread and their impact on treatment options. Here, we developed a simple, easy and rapid matrix-assisted laser desorption ionization-time of flight (MALDI-TOF)-based assay to detect carbapenemases and compared this innovative test with four other diagnostic approaches on 47 clinical isolates. Tandem mass spectrometry (MS-MS) was also used to determine accurately the amount of antibiotic present in the supernatant after 1 h of incubation and both MALDI-TOF and MS-MS approaches exhibited a 100% sensitivity and a 100% specificity. By comparison, molecular genetic techniques (Check-MDR Carba PCR and Check-MDR CT103 microarray) showed a 90.5% sensitivity and a 100% specificity, as two strains of Aeromonas were not detected because their chromosomal carbapenemase is not targeted by probes used in both kits. Altogether, this innovative MALDI-TOF-based approach that uses a stable 10-μg disk of ertapenem was highly efficient in detecting carbapenemase, with a sensitivity higher than that of PCR and microarray. © 2014 European Society of Clinical Microbiology and Infectious Diseases.


PubMed | National Cancer Center
Type: | Journal: Cancer letters | Year: 2016

Metronomic administration of chemotherapy has long been recognized as having a different biological effect from maximal tolerated dose (MTD) administration. Preclinical studies have demonstrated these differences quite elegantly and many clinical trials have also demonstrated reproducible activity albeit small, in varied solid malignancies even in patients who were heavily pretreated. However, the concept of metronomic chemotherapy has been plagued by lack of a clear definition resulting in the published literature that is rather varied and confusing. There is a need for a definition that is mechanism(s)-based allowing metronomics to be distinguished from standard MTD concept. With significant advances made in understanding cancer biology and biotechnology, it is now possible to attain that goal. What is needed is both a concerted effort and adequate funding to work towards it. This is the only way for the oncology community to determine how metronomic chemotherapy fits in the overall cancer management schema.


Jiang C.-M.,Laboratory of Clinical Pharmacology | Li G.-X.,Laboratory of Clinical Pharmacology | Xia S.-X.,Laboratory of Clinical Pharmacology | Tang S.,Laboratory of Clinical Pharmacology | And 3 more authors.
Chinese Journal of New Drugs | Year: 2011

Objective: To study the pharmacokinetics of ginsenoside Rb 1 of Shengmai injection after a single intravenous infusion with constant speed in healthy volunteers. Methods: Fifteen healthy volunteers were administered with a single intravenous infusion of 60 mL Shengmai injection. The plasma concentrations of ginsenoside Rb 1 were determined by LC/MS/MS. The pharmarcokinetic parameters of ginsenoside Rb 1 were calculated by DAS 2.1 software. Results: The plasma concentration-time curve fitted two compartment model. After single intravenous infusion of Shengmai injection, the main pharmacokinetic parameters of ginsenoside Rb 1 were as follow: C max=(10.572 ± 8.952) mg ·L -1, t 1/2=(47.983 ± 7.256) h, AUC 0~144h=(346.668 ± 267.894) mg ·h ·L -1. Conclusion: Administration of a single intravenous infusion of Shengmai injection is safe in healthy volunteers.

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