奥美拉唑肠溶胶囊人体药代动力学和相对生物利用度研究

目的 :研究奥美拉唑肠溶胶囊在健康人体内的药代动力学和相对生物利用度。方法 :采用 HPL C法测定 8名男性健康志愿受试者随机交叉一次口服康恩贝产 (受试品 ,商品名金奥康 )和瑞典产 (参比品 ,商品名洛赛克 )奥美拉唑胶囊各 40 mg的血药浓度 ,进行人体生物利用度研究。结果 :两种胶囊的药—时曲线和药代动力学特征均符合—室开放模型。测得主要药代动力学参数为 :试验胶囊和参比胶囊从胃肠吸收的滞后的时间 (L.T)分别为 1.3 6± 0 .92 h和 0 .90± 0 .42 h;Cmax分别为 0 .2 8±0 .2 0 mg/L 和 0 .3± 0 .2 0 mg/L;;Tmax分别为 3 .69± 1.46h和 2 .44± 0 .74h;AUC分别为 1.71± 1.2 0 mg/L· h和 2 .44±0 .74mg/L· h;消除半衰期分别为 2 .3 4± 0 .61h和 2 .2 2± 0 .70 h;结论 :奥美拉唑试验胶囊的相对生物利用度为 10 2 .5± 16.1%。经统计分析与参比胶囊比较为等效     

Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study

Background -  

Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC.     

Enhance transdermal delivery of flurbiprofen via microemulsions: Effects of different types of surfactants and cosurfactants

Background and the purpose of the study

Microemulsions are thermodynamically stable, clear dispersions of water, oil, surfactant, and cosurfactant. This study was aimed to develop flurbiprofen microemulsion for enhanced transdermal delivery and investigate the effects of different surfactants and cosurfactants on its delivery and phase behavior.

Method

Various surfactant-cosurfactant mixtures in ratio of 2:1 (Smix) along with oleic acid (oil) were selected and phase diagrams were constructed. Six microemulsions each containing 5% drug, 5% oil, 56% Smix and 34% water, were prepared and compared for their permeation and phase behaviors to determine the effects of the type of Smix.

Results

In vitro transdermal permeation through rabbit skin of all microemulsions was high than saturated aqueous drug solution. Tween 20 and ethanol as Smix produced the highest flux amongst all the Smix, and were used to prepare formulations with different values of oil and Smix. While the type of surfactant did not affect the droplet size, propylene glycol as cosurfactant produced the largest droplets and highest viscosity. Decrease in oil or Smix concentration resulted in decrease of the droplet size and increase in permeation flux while decrease in viscosity also increased the permeation flux of microemulsions. Finally the selected microemulsion formulation comprising 5% flurbiprofen, 5% oleic acid, 46% Tween 20:ethanol (2:1) and 44% water, showed the highest transdermal flux and caused no skin irritation.

Conclusion

Type of surfactant and cosurfactant affect both the phase behavior and transdermal drug delivery of microemulsion; and results of this study showed that they are promising vehicles for improved transdermal delivery and sustained action of flurbiprofen.     

Definitions of antiretroviral treatment failure for measuring quality outcomes

Objectives

Our aim was to compare three different definitions of treatment failure and discuss their use as quality outcome measures for a clinical service.

Methods

Data for treatment‐naïve patients who attended the Melbourne Sexual Health Centre (MSHC) between 1 January 2000 and 31 December 2008 were analysed. Definition 1 was the strict Food and Drug Administration (FDA) definition of treatment failure as determined using the time to loss of virological response (TLOVR) algorithm. Definition 2 defined treatment failure as occurring in those whose viral load never fell to <400 HIV‐1 RNA copies/mL or who developed two consecutive viral loads ≥400 copies/mL on any treatment (switching or stopping treatment with a viral load <400 copies/mL was permitted). Definition 3 was the same as definition 2 except that individuals were also deemed to have failed if they stopped treatment for 6 months or longer.

Results

There were 310 antiretroviral‐naïve patients who started treatment in the study period. Of these, 156 [50.3%; 95% confidence interval (CI) 42.1–53.3%] experienced treatment failure under definition 1, 10 (3.2%; 95% CI 1.5–5.8%) experienced treatment failure under definition 2, and 16 (4.5%; 95% CI 2.5–7.4%) experienced treatment failure under definition 3 over the 108 months of follow‐up. The probability of failing definition 1 was statistically different from the probability of failing definition 2 or 3 (P=0.01).

Conclusion

There were significant differences in treatment failure for the three definitions. If definition 1 were used, the outcomes would be sufficiently common to enable clinics to be compared but would be less meaningful. If definition 2 or 3 were used, the events would be too rare to enable clinics to be compared, but it would be possible to set a benchmark level of success that clinics could aim to reach.     

Comparison of the rehabilitation status of continuous ambulatory peritoneal dialysis and in-centre haemodialysis in Chinese patients

Summary: In Hong Kong, dialysis treatment has become more accessible in recent years. Due to a shortage of kidney donors patients are required to stay on dialysis for longer periods. the rehabilitation status of 181 end-stage renal failure (ESRF) patients on dialysis, 34 on in-centre haemodialysis (ICHD) and 147 on continuous ambulatory peritoneal dialysis (CAPD), at the Prince of Wales Hospital was studied. There was no statistically significant difference in physical functioning due to treatment type; however, CAPD patients were shown to be more socially active and had a better family life than ICHD patients (P < 0.01). There were no statistically significant correlations between physical functioning, social life or family life and the duration of dialysis in both ICHD and CAPD patients. In both groups of patients 52.9% of ICHD and 52.4% of CAPD patients had decreased employment status. All the patients were assessed by doctors-in-charge on their physical fitness for employment, 85.7% (n= 6) of the unemployed ICHD patients and 71% (n= 44) of the unemployed CAPD patients were considered to be physically fit to work. Due to the ageing of the general population and greater availability of dialysis treatment and higher survival rate of the chronically ill have led to an increase in the number of elderly patients on dialysis (aged 60 years and over). the proportion of elderly dialysis patients in our renal centre increased from 7–23% in the past 5 years. Continuous ambulatory peritoneal dialysis patients aged less than 60 years were found to be significantly more physically active and socially active than CAPD patients aged over 60 years (P < 0.01). In the aspect of a better family life for these patients, no statistically significant difference was found between the two groups. Rehabilitation of ESRF patients can be achieved by renal replacement therapy. It is concluded that CAPD patients have better adaptation in social life and family life than ICHD patients.