对贵刊刊登的《利福平(0.1%)液治疗慢性化脓性中耳炎》一文的验证

阅读了贵刊 1999年 18卷第 4期 2 2 5页刊登的“利福平 (0 .1% )液治疗慢性化脓性中耳炎”[1] 一文后 ,深受启发 ,笔者自 2 0 0 0年～ 2 0 0 1年对 96例慢性中耳炎病人进行临床验证 ,报道如下。临床资料　 96例均为本院门诊病人 ,男性 60例 ,女性 36例。年龄 (30±ｓ 6)а ,16～ 65ａ均为慢性化脓性中耳炎单纯型病人 ,左耳 5 6例 ,右耳 5 2例 ,双耳17例。病程 2 5 0ａ。治疗方法　我们采用药厂生产的利福平滴眼液 (上海集成药厂生产 ) ,配置成 0 .1%利福平滴耳液 [取包装内利福平片 1片 (每片 10ｍｇ) ,加入缓冲液10ｍＬ中 ,振荡均匀 ,即得…     

国产和进口利福平的生物利用度比较

在10名健康受试者口服利福平后2,4,6,8及11h用紫外分光光度仪测定血浆利福平浓度。在2,4,6,8,11及24h测定尿中药物的排出量。共测定3个药厂的产品,结果表明国产和进口利福平胶囊的生物利用度相似。     

复方利福平胶囊的差示－三波长分光光度测定

分别采用差示－三波长分光光度法和单波长分光光度法测定复方利福平胶囊中的异烟肼及利福平。方法简便、准确。回收率和ＲＳＤ分别为９９．７９％、９９．３４％和０．５３％、０．６７％。     

Altered Prednisolone Pharmacokinetics in Patients Treated with Rifampicin

ABSTRACT The pharmacokinetics and protein binding of prednisolone were studied in 7 patients before and after 3 weeks of rifampicin therapy. The elimination half-time for prednisolone decreased by 45±8.1% (p<0.01), and the total body clearance of prednisolone increased by 91±26% (p<0.01). The area under the time-concentration curve (AUC) of total (free plus protein-bound) prednisolone decreased by 48±7.3% (p<0.01) and of free, unbound prednisolone by 57±9.8% (p<0.01). The reduction in AUC was greater for free than for total prednisolone (p<0.05) mainly due to the non-linear nature of prednisolone protein binding. There was no significant change in the volume of distribution. Because of the marked reduction in total and especially free prednisolone, the dosage should be adjusted accordingly if prednisolone and rifampicin are prescribed concomitantly.     

Protective effect of a 50% hydroalcoholic fruit extract of Emblica officinalis against anti-tuberculosis drugs induced liver toxicity

The present report showed the hepatoprotective property of a 50% hydroalcoholic extract of the fruits of Emblica officinalis (fruit) (EO-50) against antituberculosis (anti-TB) drugs-induced hepatic injury. The biochemical manifestations of hepatotoxicity induced by rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA), either given alone or in combination were evaluated. In vitro studies were done on suspension cultures of rat hepatocytes while sub-acute studies were carried out in rats. The hepatoprotective activity of EO-50 was found to be due to its membrane stabilizing, antioxidative and CYP 2E1 inhibitory effects.     

Drug-Drug Interaction Studies on First-Line Anti-tuberculosis Drugs

The purpose of this study was to carry out drug-drug compatibility studies on pure first line anti-tuberculosis drugs, viz., rifampicin (R), isoniazid (H), pyrazinamide (Z), and ethambutol hydrochloride (E). Various possible binary, ternary, and quaternary combinations of the four drugs were subjected to accelerated stability test conditions of 40°C and 75% relative humidity (RH) for 3 months. For comparison, parallel studies were also conducted on single drugs. Changes were looked for in the samples drawn after 15, 30, 60, and 90 days of storage. Analyses for R, H, and Z were carried out using a validated HPLC method. The E was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), as it does not absorb in ultraviolet (UV). All single pure drugs were relatively stable and showed only 3%–5% degradation under accelerated conditions for 3 months. However, significant interactions were observed in case of the drug mixtures. In particular, ternary and quaternary drug combinations containing R and H along with Z and/or E were very unstable, showing 90%–95% and 70%–75% loss of R and H, respectively. In all these cases, isonicotinyl hydrazone (HYD) of 3-formylrifamycin and H was found to be the major degradation product. In case of RE and RZE mixtures, where H was absent, 3-formylrifamycin was instead the key degradation product. Another unidentified peak was observed in the mixture containing RZE. Apart from these chemical changes, considerable physical changes were also observed in pure E and the mixtures containing E, viz., RE, ZE, RHE, RZE, and RHZE. In addition, significant physical changes associated with noteworthy loss of H and E were also observed in mixtures containing HE and HZE. The present study thus amply shows that the four primary anti-tuberculosis drugs, when present together, interact with each other in a multiple and complex manner.     

利福平聚乳酸-羟基乙酸共聚物纳米粒雾化吸入给药肺靶向性研究

目的研究利福平聚乳酸-羟基乙酸共聚物纳米粒雾化吸入给药的肺靶向性。方法分别将利福平聚乳酸-羟基乙酸共聚物纳米粒混悬液(RFP-PLGA-NPs)和利福平注射液(RFP-Sol)以雾化吸入方式给予SD大鼠,在不同时间点测定利福平在大鼠肺组织中的浓度,计算相应药动学参数,比较2种制剂在肺组织中药动学过程,并评价靶向性。结果 RFP-Sol和RFP-PLGA-NPs的Tmax分别为(1.50±0.01)h和(2.00±0.08)h,Cmax分别为(0.83±0.07)mg.L 1和(5.02±0.05)mg.L 1,AUC0→∞分别为(6.24±0.24)mg.h.L 1和(35.80±6.34)mg.h.L 1,CL分别为(4.801±0.18)L.h 1.kg 1和(0.85±0.15)L.h 1.kg 1。通过对re和Ce等靶向性指标进行分析,RFP-PLGA-NPs在肺组织中的re和Ce均>1。结论与RFP-Sol相比,RFP-PLGA-NPs经雾化吸入给药后,明显提高了肺组织中药物的分布并且延缓消除,有显著的缓释性,从而降低药物对全身的不良反应,提高对肺结核的治疗作用。