摘要:眼部的局部给药方式影响着药物作用的强度,速率及持续时间和不良反应。视网膜,脉络膜,玻璃体及视神经的疾病则对眼后节的局部给药治疗提出了挑战,以局部给药的方式通过解剖学的膜屏障及泪液排泄,并达到在特定部位起治疗作用的药物浓度是其中的重要课题。全身给药则难以在眼组织积蓄足够的药物浓度,且易引起全身性的不良反应。眼表局部应用滴眼剂在泪液循环及角膜,结膜的屏障作用下易发生流失,而有创的给药方式包括玻璃体内注射,结膜下注射等变得越来越普遍的同时,除对病人造成疼痛不适外,甚至也可导致多种严重于疾病本身的并发症。本文综述了近几年来随着各种眼科疾病分子机制的研究和解明,眼部局部给药方式及新剂型的药代动力学及安全性的研究进展。Abstract: The ocular drug delivery system affects the drug’s efficacy,rate of speed,velocity and adverse reaction.How to deliver the drug with therapeutic local concentrations to the posterior segment remains a challenge. Many invasive methods such as intravitreal injection,subconjunctival injection are generally used,noninvasive method like eye drop can not pass through the barrier of the eye although it is convenient.The recent progress in safty and pharmacokinetic of ocular drug delivery system is reviewed in this article.
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）
摘要:目的:建立测定复方氯唑沙宗片中氯唑沙宗血药浓度的方法,并进行其在健康人体药物动力学研究。方法:18名男性健康志愿者单剂量口服复方氯唑沙宗片,高效液相色谱法测定复方氯唑沙宗中氯唑沙宗的血药浓度。结果和结论:此法操作简便、结果可靠。复方氯唑沙宗片中的氯唑沙宗主要药物动力学参数分别为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).
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.
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.