Objective To observe the change of diffusion upper limit of macromol ecules through pathological retina and the difference between the layers of retina. Methods Retinal edema was emulated by establishing branch retinal vein occlusion (RVO) model in miniature pig eyes under photodynamic method. Two days later, the retinas of both eyeballs were peeled off. The diffusion test apparatus was designed by ourselves. FITC-dextrans of various molecular weights (4.4, 9.3, 19.6, 38.9, 71.2 and 150 kDa) and Carboxyfluorescein (376 Da) were dissolved in RPMI1640 solutions and diffused through inner or outer surface of retina. The rate of transretinal diffusion was determined with a spectrophotometer. Theoretical maximum size of molecule (MSM) was calculated by extrapolating the trend-linear relationship with the diffusion rate. In separate experiments to determine the sites of barrier to diffusion, FITC-dextrans were applied to either the inner or outer retinal surface, processed as frozen sections, and viewed with a fluores cence microscope. Results FITC-dextrans applying to inner retinal surface, 4.4 kDa dextrans were largely blocked by inner nuclear layer (INL); 19.6,71.2 kDa dextrans were blocked by the nerve fiber layer (NFL) and inner plexiform layer; 15.0 kDa dextrans were blocked by NFL. FITC-dextrans applying to outer retinal surface, most dextrans with various molecular weights were blocked before outer nuclear layer (ONL). No matter applying to the inner or outer surface, Carboxyfluore scein can diffuse through the whole retina and aggregate at INL and ONL. After RVO, the inner part of retina became edema and cystoid, loosing the barrier function. Compared with the normal retina, the MSM in RVO tissues increased (6.5plusmn;0 39nm Vs 6.18plusmn;0.54nm, t=4.143, P=0.0001). Conclusions A fter RVO, the barrier function of inner part of retinal is destroyed and the upper limit of diffusion macromolecule size increased, which is nevertheless limited. ONL acts as bottle-neck barriers to diffusion, if the outer part of retina is damaged, the change of the diffusion upper limit will be prominent. （Chin J Ocul Fundus Dis，2008，24：197-201）
Exercise has been increasingly recognized in clinical guidelines as a recommended component of rehabilitation for people with hemophilia (PWH), with evidence supporting appropriate physical activity’s multifaceted benefits. During exercise, the bleeding risk in PWH exhibits a critical correlation with circulating clotting factor activities, where higher factor concentrations demonstrably reduce hemorrhagic events. However, economic constraints limit universal access to high-dose prophylactic clotting factor replacement therapy. Through pharmacokinetics (PK) monitoring of clotting factor, clinicians can strategically tailor exercise types and frequencies, or adjust factor replacement dosages based on activity-specific demands. This individualized approach not only enhances the cost-effectiveness of clotting factor utilization, but also improves safety by mitigating bleeding risks. This article examines the feasibility and recent advancements in PK-guided individualized physical activity prescriptions for PWH, presenting evidence-based insights to inform clinical practice and future research priorities.
摘要:目的:建立測定復方氯唑沙宗片中氯唑沙宗血藥濃度的方法,并進行其在健康人體藥物動力學研究。方法:18名男性健康志愿者單劑量口服復方氯唑沙宗片,高效液相色譜法測定復方氯唑沙宗中氯唑沙宗的血藥濃度。結果和結論:此法操作簡便、結果可靠。復方氯唑沙宗片中的氯唑沙宗主要藥物動力學參數分別為T1/2 （0927±03747） h,Tmax （1403±0681） h,Cmax （21063±5748） mg/L,AUC0~6 （51624±15202） mg/(L·h),AUC0~ （53201±15142） mg/(L·h)。Abstract: Objective: Aim To investigate the pharmacokinetics of complex chlorzoxazone tablets in healthy volunteers.Methods:Eighteen male healthy subjects received a single dose of two pieces of complex chlorzoxazone tablets.The concentration of complex chlorzoxazone was determined by HPLC.Results and Conclusion: This study provided a simple and reliable assay which can be used to determine two component concentrations of complex chlorzoxazone tablets in human serum. The main pharmacokinetic parameters of chlorzoxazone was as follows:T1/2 （0927±03747）h,Tmax （1403±0681）h,Cmax （21063±5748） mg/L,AUC0~6 （51624±15202） mg/(L·h),AUC0~5 （3201±15142） mg/(L·h).
Population pharmacokinetics is a research technique based on computer simulation and data analysis, and it has been employed to investigate the dynamic behavior of drug metabolism in different populations. This approach could address practical challenges such as prolonged clinical trial durations, high costs, and increased difficulty in traditional clinical trials. By comprehensively analyzing differences in the internal drug metabolism processes across populations with varying physiological and pathological conditions, population pharmacokinetics has emerged as an effective method to optimize drug development and clinical applications. This article provides a preliminary overview of the essence of population pharmacokinetics, its application in clinical trials, and potential future trends. We hope to serve as a reference and guidance for the application of new technologies and methods in clinical trials.
Paclitaxel (PTX)-loaded self-assembling nano-micelles (PTX/NMs) were prepared based on amphiphilic cholesterol-bearing γ-polyglutamic acid (γ-PGA-graft-CH). The properties of PTX/NMs in vitro and in vivo were investigated. The results indicated that PTX could be entrapped in γ-PGA-graft-CH NMs. PTX/NMs was characterized with a size of (343.5 ± 7.3) nm, drug loading content of 26.9% ± 0.8% and entrapment efficiency of 88.6% ± 1.7% at the optimized drug/carrier ratio of 1/10, and showed a pH-sensitive sustainable drug-release and less cytotoxicity in vitro. In vivo release and the pharmacokinetics study in mice showed that the elimination half-life (t1/2β) and area under curve (AUC) of PTX/NMs were significantly higher than those of PTX/polyoxyethylene castor oil (PTX/PCO), and less clearance (CL) of PTX/NMs was also observed. PTX/NMs were distributed higher in liver and tumor than PTX/PCO, and showed a good tumor-inhibiting activity in tumor-bearing mice. This study would lay a foundation on the potential application of γ-PGA-graft-CH NMs were the antitumor drug-delivery.
