Pricing of drugs and donations: options for sustainable equity pricing

Effective medicines exist to treat or alleviate many diseases which predominate in the developing world and cause high mortality and morbidity rates. Price should not be an obstacle preventing access to these medicines. Increasingly, drug donations have been established by drug companies, but these are often limited in time, place or use. Measures exist which are more sustainable and will have a greater positive impact on people's health. Principally, these are encouraging generic competition; adopting into national legislation and implementing TRIPS safeguards to gain access to cheaper sources of drugs; differential pricing; creating high volume or high demand through global and regional procurement; and supporting the production of quality generic drugs by developing countries through voluntary licenses if needed, and facilitating technology transfer.     

老年肺癌患者呼吸道深部真菌感染因素分析

目的：探讨老年肺癌患者呼吸道深部真菌感染的危险因素及预防措施。方法：对58例老年肺癌患者呼吸道深部真菌感染的临床资料进行回顾性分析。结果：老年肺癌患者呼吸道深部真菌感染的病原菌以白色念珠菌为主，占72，4％（42／58）。肺癌的分期晚、白细胞减少、长期应用多种抗生素、放化疗及各种侵入性诊疗等为真菌感染的危险因素。应用以氟康唑为主的综合治疗后，52例（89．7％）治愈，6例死亡。结论：老年肺癌患者呼吸道深部真菌感染有多种危险因素，应早期预防，早期诊断，确诊后及时应用高效低毒的氟康唑治疗有较好的疗效，同时应加强免疫与支持疗法。     

Interference of antimycotics and other drugs with methohexital hypnosis in rats

Compounds of various pharmacological and chemical classes were studied for their interaction with methohexital hypnosis. Rats were treated daily for 5 days with an oral dose of a test compound or solvent. On days 1, 5, and 8 methohexital was injected intraperitoneally and the duration of hypnosis was measured. Three types of interaction with methohexital hypnosis were observed. Acute prolongation of hypnosis on day 1 was the most marked effect of fluconazole (median effective dose, ED₅₀: 8.66 mg/kg), but this occurred also with phenobarbital (ED₅₀: 26.4 mg/kg) and diphenylhydantion (ED₅₀: ～ 160 mg/kg). Tolerance to prolongation, i.e., a decrease of the hypnosis time by more than 50% from day 1 to day 5, was most marked with phenobarbital (ED₅₀: 12.6 mg/kg) and diphenylhydantion (ED₅₀: 113 mg/kg) but was also found with fluconazole (ED₅₀: 22.6 mg/kg). Shortened hypnosis times on day 8 occurred with phenobarbital (ED₅₀: ～ 40.0 mg/kg) and diphenylhydantoin (ED₅₀: ～ 160 mg/kg). The antimycotic itraconazole, the antidiarrheal loperamide, the thymosthenic agent ritanserin, and the antiallergics astemizole and levocabastine were devoid of interactions with methohexital. When compared with the basic activity of the tested compounds in rats, interference with methohexital hypnosis was most pronounced with phenobarbital (ratio 3.13) followed by fluconazole (ratio: 3.28) and diphenylhydantoin (ratio: 5.07).     

高效液相色谱法测定氟康唑胶囊中氟康唑的含量

目的建立高效液相色谱法测定氟康唑胶囊中氟康唑的含量。方法采用ODS(KromailC18,4 6mm× 2 5 0mm)色谱柱 ,以乙腈 - 0 0 1mol/L磷酸盐缓冲液 (2 5∶75 )为流动相 ,以非那西丁为内标 ,测定氟康唑的含量。结果线性为 0 0 33～ 0 33mol/L ;回收率为 99 1% ;RSD为 0 94 % (n =5 )。结论本方法可有效控制产品质量     

Evaluation of biofilm formation ability in different Candida strains and anti-biofilm effects of Fe3O4-NPs compared with Fluconazole: an in vitro study

Objective

Biofilm formation ability is one of the major virulence factors contributing to the pathogenesis of Candida species. Biofilms produced by Candida spp. cause complicated treatments and contribute to increasing unpleasant mortality rates. Nanoparticles of Fe₃O₄ (Fe₃O₄-NPs) are considered due to their magnetic and biochemical properties, as well as their low costs. The purpose of present study was to determine biofilm formation ability in different Candida strains and evaluation of anti-biofilm effect of Fe₃O₄-NPs compared with FLC.

Antifungal Activity of Propolis Against Yeasts Isolated From Blood Culture: In Vitro Evaluation

Background: Due to the failure of available antifungal agents in the treatment of candidemia and the toxic activities of these drugs, a lot of researches are being conducted to develop new nontoxic and effective antifungal agents for optimal control of fungal pathogens. The aim of this study is to evaluate the in vitro antifungal activity of propolis against yeasts isolated from the blood cultures of intensive care unit patients. Methods: Seventy‐six strains were included in this study. The in vitro antifungal activity of propolis, fluconazole (FLU), and itraconazole (ITR) was investigated by the microdilution broth methods (CLSI guidelines M27‐A3 for yeast). The propolis sample was collected from Kayseri, Turkey. Results: Of the 76 isolates, 33 were identified as Candida albicans while 37 were C. parapsilosis, three were C. tropicalis, and three were identified as C. glabrata. The geometric mean range for MIC (μg/ml) with regard to all isolates was 0.077 to 3 μg/ml for FLU and ITR, and 0.375 to 0.70 μg/ml for propolis. It was shown that propolis had significant antifungal activity against all Candida strains and the MIC range of propolis was determined as 0185 to 3 μg/ml. Conclusion: This study demonstrated that propolis had significant antifungal activity against yeasts isolated from blood culture compared with FLU and ITR. The propolis MIC in azole‐resistant strains such as C. glabrata was found lower than the FLU MIC.     

伊曲康唑和氟康唑在预防肺移植术后曲霉菌感染的疗效比较

目的探讨预防肺移植术后曲霉菌感染的药物疗效。方法 2003年7月～2010年4月,为38例患者实行肺移植手术,应用伊曲康唑,氟康唑在预防肺移植术后曲霉菌感染的临床效果和在卫生经济学方面来比较和评价。结果应用伊曲康唑比应用氟康唑在预防肺移植术后曲霉菌感染的发生率明显降低(P=0.002)。并且可以减少肺移植术后患者并发曲霉感染的风险,降低相应的治疗费用,有效的节约社会医疗资源。结论应用伊曲康唑和二性霉素B雾化在对肺移植术后的早期曲霉菌感染的预防和治疗中是相对有效的。     

Effects of the moderate CYP3A4 inhibitor, fluconazole, on the pharmacokinetics of fesoterodine in healthy subjects

AIMS

To assess the effects of fluconazole, a moderate CYP3A4 inhibitor, on the pharmacokinetics (PK) and safety/tolerability of fesoterodine.

METHODS

In this open-label, randomized, two-way crossover study, 28 healthy subjects (18–55 years) received single doses of fesoterodine 8 mg alone or with fluconazole 200 mg. PK endpoints, including the area under the plasma concentration–time curve from 0 to infinity (AUC(0,∞)), maximum plasma concentration (C_max), time to C_max (t_max), and half-life (t_1/2), were assessed for 5-hydroxymethyl tolterodine (5-HMT), the active moiety of fesoterodine.

RESULTS

Concomitant administration of fesoterodine with fluconazole increased AUC(0,∞) and C_max of 5-HMT by approximately 27% and 19%, respectively, with corresponding 90% confidence intervals of (18%, 36%) and (11%, 28%). There was no apparent effect of fluconazole on 5-HMT t_max or t_½. Fesoterodine was generally well tolerated regardless of fluconazole co-administration, with no reports of death, serious adverse events (AEs) or severe AEs. Following co-administration of fesoterodine with fluconazole, 13 subjects (48%) experienced a total of 40 AEs; following administration of fesoterodine alone, six subjects (22%) experienced a total of 19 AEs. The majority of AEs were of mild intensity. There were no clinically significant changes in laboratory or physical examination parameters.

CONCLUSION

Fesoterodine 8 mg single dose was well tolerated when administered alone or with fluconazole. Based on the observed increase in 5-HMT exposures being within the inherent variability of 5-HMT pharmacokinetics, adjustment of fesoterodine dose is not warranted when co-administered with a moderate CYP3A4 inhibitor provided they are not also inhibitors of transporters.     

华法林与氟康唑联合应用致国际标准化比值升高

1例72岁女性患者因可疑肺栓塞给予华法林及那屈肝素钙联合治疗,国际标准化比值(INR)稳定在1.23～2.81。联合用药8 d后,停用那屈肝素钙,单用华法林3 mg/d口服2 d后,检查INR为3.31。因行痰培养检查示白色念珠菌阳性,遂加用氟康唑0.4 g,1次/d静脉滴注,且华法林剂量调整为1.5 mg/d。氟康唑与华法林联用后第1、6天INR分别为3.91,7.31。立即停用华法林,氟康唑继续按原剂量应用,并给予维生素K1 40 mg肌内注射。停药后第1、2、3天INR分别为4.91,2.01,1.30。停药后第5天再次应用华法林1.5 mg/d,同时氟康唑调整至0.2 g/d。两药联用后第4天INR为1.68。     

氟康唑片粉末压片工艺研究及溶出度测定

目的 对氟康唑片粉末压片工艺进行研究,以提高氟康唑的稳定性和溶出度.方法采用粉末直接压片工艺制备,选择适合粉末直接压片的辅料制备片剂.结果经溶出度测定,制剂可达到药典中氟康唑的溶出度要求,初步稳定性研究表明样品稳定性较好.结论粉末压工艺制备的氟康唑片稳定性好,溶出度符合各项要求.