Aim: To evaluate the single-and multiple-dose pharmacokinetics of vincristine sulfate liposomes (VSLI) in patients with advanced solid tumors. Methods: In single-dose pharmacokinetic study, 16 patients were administered VSLI (1.5, 2.0, or 2.3 mg·m -2 ) through intravenous infusion. Another 6 patients receiving vincristine sulfate (VCR, 2.0 mg) were taken as the control. In multiple-dose pharmacokinetic study, 12 patients were administered VSLI (1.5 or 1.8 mg·m -2 ) through intravenous infusion weekly for 4 consecutive weeks. The plasma concentration of VSLI was determined using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Results: After intravenous infusion of the single dose of VSLI, the plasma concentrations were characterized by bi-exponential decline curves. No statistically significant differences were observed between the main pharmacokinetic parameters in the 3 dose groups. Compared with the patients receiving VCR, the patients treated with VSLI displayed an increase in the area under the plasma concentration vs time curve (AUC), and a decrease in plasma clearance rates. On the 4th cycle in the multiple-dose study, the plasma concentration of VCR in all subjects prior to the weekly administration was below the lower limit of quantification (LLOQ). The calculated pharmacokinetic parameters from the subjects in the multiple-and single-dose (1.5 mg·m -2 ) groups had no significant differences. Although the administration of liposomal VCR may significantly elevate the plasma concentration of VCR, VSLI-associated adverse events were similar to those associated with conventional VCR. Conclusion: VSLI exhibits a lower clearance and a higher AUC compared with conventional VCR. No accumulation was observed in patients exposed to VSLI for 4 consecutive weeks. VSLI was generally tolerated in the subjects. The phase II dose of VSLI may be recommended as 4 doses of 1.5 mg·m -2 for treatment of patients with advanced solid tumors.

npg IntroductionGinseng has long been known to be multifunctional as both a tonic and a sedative agent. Ginsenosides, the main bioactive components of Ginseng, have become a major focus in cancer research.Based on the properties of different sapogenins, ginsenosides are divided into 3 groups, 20(S)-protopanaxadiol, 20(S)-protopanaxatriol and oleanolic acid glycoside. Many ginsenosides have been found to have anti-cancer activity [1] and are involved in several anti-cancer mechanisms, such as inhibition of cell proliferation [2] , invasion [3] , induction of cell apoptosis [4] and anti-angiogenesis [5] . However, the antitumor mechanism of ginsenoside is not fully clear. Nakata H et al reported that ginsenoside Rh2 inhibited the growth of human ovarian cancer cells cultured in nude mice [6] . Quasipanaxatriol may reverse daunomycin resistance in P388/ADM cells by effectively blocking daunomycin efflux, leading to the accumulation of the drug in the cells [7] . Ginsenoside has been implicated in several signaling pathways, such as MAPK [8] , caspase [9] , NF-kappaB, and JNK pathways [10] . Furthermore, ginsenoside Rg3 ("Shenyi" Capsule) has shown effects on improving body immunity, decreasing toxic effects induced by chemotherapy Aim: To evaluate single-dose and multiple-dose pharmacokinetics of panaxatrol disuccinate sodium in healthy volunteers and patients with advanced solid tumors. Methods: In the single-dose pharmacokinetic study, 27 healthy volunteers received panaxatrol disuccinate sodium in three doses (70, 100, and 140 mg·m -2 ). In the multiple-dose pharmacokinetic study, Panaxatrol disuccinate sodium was administered to 8 patients at 100 mg·m -2 daily in a 30-day continuous intravenous injection. Determination of the panaxatrol disuccinate sodium plasma concentration was performed by an LC-MS method. The pharmacokinetic analysis system -Drug and Statistics (DAS) -was applied to assess plasma panaxatrol disuccinate sodium concentration-time data. Results: After a single intravenous dose of 70, 100, or 140 mg·m -2 was administered to subjects, panaxatrol disuccinate sodium distributed broadly, and the plasma concentration of panaxatrol disuccinate sodium declined rapidly. No significant differences were observed in the main pharmacokinetic parameters among the three dosing groups, including AUC 0-t , MRT 0-t , VRT 0-t , t 1/2Z , CL z/F , V z/F , and C 0 (P>0.05). In the multiple-dose pharmacokinetic study, the mean steady-state peak concentration (C max ), trough concentration (C min ), average concentration (C av ), mean steady state AUC (AUC ss ) and the degree of fluctuation were 13.96±15.48 mg·L -1 , 0.18±0.29 mg·L -1 , 0.15±0.29 mg·L -1 , 3.58±6.94 mg·L -1 ·h, and 148.00±117.18, respectively. At any given dose of panaxatrol disuccinate sodium, interindividual variability in the pharmacokinetic parameters was obvious. Conclusion: The effect of the dose level on single-dose pharmacokinetics of panaxatrol disuccinate sodium was not significant. No accumulation was observed with exposure to 100 mg·m -2 ...

This paper presents an invertebrate leg-like mechanism, which is biologically inspired from invertebrate creatures such as crabs and insects. For the purpose that the leg mechanism could imitate the behavior of the invertebrate animal on rough terrain, it should have the same degree of freedom as the crabs or insects have. The novel leg mechanism consists of 3 joints which linkage has 5 degrees of freedom (DOFS), and mainly depends on a coxa joint driven by a parallel mechanism for the biomimetic motions. The parallel mechanism with 3 DOF is well designed and implemented with the excellent kinematical performances as invertebrate creatures. The mathematical model of the leg mechanism and the kinematical analysis are described, and static force performance characteristics are also discussed. The kinematical performances of the leg mechanism are analyzed by the numerical simulation conducted in biomimetic robots application. The simulation results show the performance of the proposed leg-like mechanism and verify that the leg can be used in the biomimetic robot which could exactly imitate limb motions.