氧氟沙星片的药物动力学和生物利用度

在８例健康志愿者中进行国产与进口氧氟沙得片药物动力学和生物利用度研究。随机交叉试验设计单剂量口服４００ｍｇ，用ＨＰＬＣ测定血药浓度，按非室模型计算，求得２种制剂各项药物动力学参数，无显著性差异（Ｐ＞０．０５），以进口药片为标准（Ｆ＝１）求得国产药片的相对生物利用度为９２．２％。     

罗红霉素胶囊剂的临床药物动力学及相对生物利用度

目的：进行国产与进口罗红霉素的生物利用度研究。方法：通过交叉试验对８名男性志愿者（２２．６ａ±ｓ２．１ａ）交叉口服罗红霉素３００ｍｇ国产胶囊剂和进口片剂,进行单剂量药物动力学研究。血药浓度采用微生物法进行测定。结果：口服国产胶囊和进口片剂的血药浓度＿时间曲线均符合二室模型,Ｃｍａｘ分别为９．５ｍｇ／Ｌ±１．３ｍｇ／Ｌ与９．０ｍｇ／Ｌ±１．０ｍｇ／Ｌ,Ｔｍａｘ为１．１４ｈ±０．１８ｈ与１．３１ｈ±０．２１ｈ,Ｔ１２β为１３．１ｈ±２．４ｈ与１３．６ｈ±２．２ｈ,ＡＵＣ为１０７ｍｇ·ｈ／Ｌ±２３ｍｇ·ｈ／Ｌ与１０８ｍｇ·ｈ／Ｌ±１４ｍｇ·ｈ／Ｌ。比较２种制剂的药物动力学参数,其差别均无显著意义（Ｐ＞０．０５）。与进口罗红霉素片相比较,国产罗红霉素胶囊剂的相对生物利用度为（９８±１３）％。口服该药４８ｈ尿药回收率为给药量的（１５±５）％。结论：国产罗红霉素胶囊体内过程与进口罗红霉素片剂相仿,２种制剂生物等效。     

吲哚美辛缓释胶囊人体药物动力学与生物利用度

目的：研究吲哚美辛（Ｉｎｄ）缓释胶囊在正常人体内的药物动力学和相对生物利用度。方法：采用ＲＰ－ＨＰＬＣ测定Ｉｎｄ的血药浓度，研究１８名健康志愿受试者单剂量ｐｏ１５０ｍｇ国产与进口Ｉｎｇ缓释胶囊的后的人体内药物动力学和相对生物利用度。结果：两种制剂的ｔｍａｘ、Ｃｍａｘ和ＡＵＣ０→∞均无显著差异（Ｐ〉．０５）；国产Ｉｎｄ缓释胶囊的相对生物利用度为１０３．０２％。结论：两种制剂为生物等效。     

格列吡嗪片在兔体内有药物动力学及相对生物利用度研究

用反相高效液相色谱法测定格列吡嗪的血药浓度，对国产和意大利格列吡嗪片在兔体内的药物动力学及其生物利用度进行了对比测定，结果表明，两种片剂的体内过程基本相同，各项药物动力学参数经ｔ检验均无显著性差异（Ｐ＞０．１）。国产片对进口片的生物利用度为８８．９８％。     

国产盐酸硫利哒嗪片的相对生物利用度及其药物动力学

本文报道利用反相ＨＰＬＣ法测定血清中的盐酸硫利哒嗪浓度，并对１０名健康志愿者口服国产与进口片后的药物动力学与生物利用度进行了考察。结果表明，国产片与进口片的各项药动学参数基本一致，经统计学分析差异无显著性（Ｐ〉０．０５），国产片相对于进口片的生物利用度为１０８．９％。     

氧氟沙星的人体生物利用度及药物动力学研究

氧氟沙星的人体生物利用度及药物动力学研究王锐，孙春华，李可欣，曹国颖（北京医院，北京１００７３０）用国产氧氟沙星（ＯＦＬＸ，北京制药厂，商品名奥复星）２００ｍｇ片剂与进口ＯＦＬＸ（商品名泰利必妥）做生物利用度及药物动力学研究。受试者为８名健康男性，采...     

国产氧氟沙星颗粒剂生物利用度的研究

本文在８名男性健康志愿者中，对国产氧氟沙星颗粒剂与进口氧氟沙星片剂进行了生物利用度的比较研究。交叉试验设计，口服给药２００ｍｇ，用专一性强、灵敏度高的反相ＨＰＬＣ－荧先检测法，测定氧氟沙星血药浓度。氧氟沙星口服给药的药时曲线均符合二室模型，其主要药动力学参数，国产颗粒剂和进口片剂分别为：ＡＵＣ１７．２１±１．５３５和１６．６４±１．７２３μｇ·ｈ／ｍｌ、Ｃ（ｍａｘ）２．９７８±０．５４５６和２．５８８±１．１９１μｇ／ｍｌ、Ｔ（ｍａｘ）０．３７００±０．２２２９和０．８１６１±０．５７８４ｈ，其相对生物利用度为１０３．４３％。经统计学处理，二者的ＡＵＣ、Ｃ（ｍａｘ）、Ｔ（ｍａｘ）均无显著性差异（ｐ＞０．０５）。结果表明，国产氧氟沙星颗粒剂在人体内的生物利用度与进口氧氟沙星片剂相似。     

Pharmacokinetics of bendazac lysine in 10 Chinese young men

比较国产和进口苄达赖氨酸（ＢＬ）片在人体内的药物动力学．方法：１０名男性汉族健康志愿者随机交叉口服单剂量５００ｍｇ国产和进口苄达赖氨酸（ＢＬ）片剂后，用高效液相紫外法测定血浆药物浓度．结果：血药浓度时间曲线拟合表明该药体内过程符合口服二室开放模型，国产和进口片剂的主要药代动力学参数：Ｃｍａｘ６６±１６ａｎｄ６５±８ｍｇ·Ｌ－１；Ｔｍａｘ０９８±０２２ａｎｄ０９８±０２１ｈ；Ｔ１２β６２±１８ａｎｄ６２±１７ｈ；ＡＵＣ３３５±４７ａｎｄ３３７±５８ｍｇ·ｈ·Ｌ－１．经ｔ检验无显著性差异，国产片对进口片的相对生物利用度为９９±１２％．结论：两种片剂具有生物等效性．     

进口和国产索他洛尔片剂的相对生物利用度研究

目的：本文对进口和国产索他洛尔片剂在１２名男性健康志愿者中的药物动力学和相对生物利用度进行了研究。方法：建立了一个检测血清中索他洛尔浓度的反相高效液相色谱－荧光检测法。结果：单剂量口服索他洛尔１６０ｍｇ后的血药浓度数据用３Ｐ８７药物动力学程序进行模型拟合，国产片剂ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ、Ｔ１／２分别为１６．２±３．６ｈ·μｇ·ｍｌ－１，１．２±０．２μｇ·ｍｌ－１，２．１±０．７ｈ，１７．０±７．２ｈ；进口片剂ＡＵＣ、Ｃｍａｘ、Ｔｍａｘ、Ｔ１／２分别为１５．９±３．５ｈ·μｇ·ｍｌ－１，１．２±０．４μｇ·ｍｌ－１，２．１±０．６ｈ，１８．６±９．４ｈ。国产片剂的相对生物利用度为１０３．５％。结论：两种片剂的所有药动学参数经统计学（ＳＰＳＳ软件）处理差异均无显著性（Ｐ＞０．０５）。     

国产麦白霉素正常人生物利用度研究

本文在８例健康成人男性志愿者中进行了进口麦迪霉素与国产麦白霉素生物利用度比较研究，交叉试验设计，口服给药６００ｍ，血清中药物浓度用微生物法测定。结果表明：两种药物从吸收、分布、排泄上都无显著性差异，国产麦白霉素相对生物利用度为１０９．５５％，根据所得药代动力学参数，从生物利用度角度对国产麦白霉素质量进行评价。     

Bioavailability and pharmacokinetics of oral ofloxacin formulations in normal subjects.

The relative bioavailability and pharmacokinetics of ofloxacin tablets and a reference oral solution of ofloxacin were compared in 32 normal male subjects using a randomized two-way crossover design. After an overnight fast, subjects were randomized to receive a single 200 mg or 300 mg dose of ofloxacin (tablet or solution) and blood samples were obtained prior to and 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 72, 96, and 120 hours after the dose. After a 5-day wash-out period, subjects were administered the same dose but of the other formulation, and blood samples were collected in an identical manner. Plasma concentrations of ofloxacin were determined by high-pressure liquid chromatography. The results showed that ofloxacin tablets were more slowly absorbed when compared to the solution and mean peak plasma concentrations were obtained in about 1.5 hours for the tablet preparation. Maximum plasma concentrations were higher after administration of the solution (Cmax = 2.24 micrograms/ml, 200 mg; Cmax = 3.25 micrograms/ml, 300 mg) compared to the tablet (Cmax = 1.74 micrograms/ml, 200 mg; 2.61 micrograms/ml, 300 mg). The bioavailability of ofloxacin tablets was greater than 98% compared to the solution. The other pharmacokinetic parameters were similar between the two dosage formulations. Ofloxacin tablets revealed an apparent volume of distribution of 1.5 l/kg, an elimination half-life of 5.6 hours, and a total clearance of 251 ml/min. In addition, a linear increase in plasma concentrations was observed when the dose of ofloxacin was increased. In summary, ofloxacin tablets was found to be reliably bioavailable and bioequivalent to the reference solution.     

Relative bioavailability studies on two tablet preparations of ofloxacin

Comparative bioavailability of two tablet dosage forms of ofloxacin (either as Hoechst (India) or Ranbaxy preparation) was investigated. In a randomized cross-over study, eight healthy human volunteers received single 200 mg dose of film coated ofloxacin in fasting state. The concentrations of ofloxacin in the collected saliva and serum samples were measured by high performance liquid chromatography. No significant difference in bioavailability of both preparations was judged from various serum and saliva pharmacokinetic parameters such as peak concentration, time to peak concentration and area under the curves. Intersubject variation was also found to be insignificant. Department of Pharmaceutical Sciences, Doctor Harisingh Gour Vishwavidyalaya (Formerly University of Saugar) SAGAR 470 003 (M.P.) India     

The bioavailability of ofloxacin from several formulations

The bioavailability of ofloxacin after a single dose of one of two tablet formulations (200 or 400 mg) or a liquid formulation (1.67 mg/ml) was investigated in 24 healthy male volunteers in an open randomized, crossover design study with a 5-day wash-out period between doses. Plasma concentrations of ofloxacin were determined at various times after administration by a sensitive and specific High Pressure Liquid Chromatography (HPLC) method. Ofloxacin was well absorbed after each administration, although somewhat more slowly after the tablet formulations than the solution. Mean AUC values of 31.8, 31.3, and 31.3 micrograms.hr/ml were calculated after administration of the solution, 2 x 200 mg tablets and a 400 mg tablet, respectively. Thus, the bioavailability of the tablets was in excess of 98% that of the liquid reference. Mean Cmax values of 4.4, 3.7 and 3.7 micrograms/ml were observed at Tmax values of 0.8, 1.6 and 1.8 hours after administration of the solution, 2 x 200 mg tablets and a 400 mg tablet, respectively. The drug was well tolerated and no adverse effects necessitating subject withdrawal were noted during the study.     

Photoreactivity of biologically active compounds. XVIII. Photostability of ofloxacin in the solid state and in a tablet formulation

The photostability of ofloxacin in the solid state has been investigated. The change in colour of uncoated and film coated ofloxacin tablets and compressed ofloxacin was studied as a function of irradiance level and total exposure energy. The degradation of ofloxacin in the various preparations was quantified by HPLC and the antimicrobial activity was determined for selected tablets. The structure of two main degradation products from ofloxacin in the solid state has been postulated from LC-MS analysis. Both products have an absorption cut-off below 400 nm and cannot explain the observed change in tablet colour. There was no apparent relationship between the change in colour and the loss of active substance or antibacterial activity for the preparations investigated. The change in colour was easily detectable at rather low exposure levels. Apparently, there was a difference in light sensitivity between the two film-coated tablet batches investigated. The results obtained were partly dependent on the conditions within the radiation chamber (e.g., exposure time and irradiance level), which emphasizes the importance of testing the samples under various conditions unless the results are unequivocal. The tablets were sensitive to visible light although ofloxacin only has a neglectible absorption above 400 nm. The film coated ofloxacin tablets did, however, absorb above 400 nm with a cut-off at approximately 520 nm. A change in tablet coating to include a component that filters visible light in addition to UV radiation might provide a solution to the discolouration problem and prevent batch to batch variations with respect to light sensitivity.     

Relative bioavailability of ofloxacin tablets in comparison to oral solution

Single oral doses of solution and tablet preparations of 300 mg ofloxacin were given to 13 healthy male volunteers in an open, randomized crossover study. Concentrations of the unchanged drug were monitored at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a 1-week washout period. Drug concentrations were measured both by a specific high pressure liquid chromatography (HPLC) method and a microbiological assay. A linear distribution independent regression analysis for method comparisons was calculated and good agreement between the two methods was found. Medians of maximum serum concentrations (Cmax) of ofloxacin after oral solution and tablet form were 5.0 mg/l and 3.5 mg/l, respectively. The times to maximal serum concentration (tmax) were 0.5 hr and 1.0 hr, respectively. The lower Cmax and later tmax after the tablet form were both statistically (p less than 0.05) different when compared to the corresponding values after the oral solution. However, the areas under the serum concentration-time curves (AUC0-28), as also the urinary recoveries did not differ significantly, showing that only the speed of absorption, but not the bioavailability of the tablet is changed in comparison to the oral solution form. Long-lasting, clinically relevant urine concentrations of ofloxacin were observed after both forms until the last collecting fraction (36 to 48 hours after medication). General tolerability was good; no side-effects were reported.     

Bioequivalence of a propylene glycol-based liquid dapsone preparation and dapsone tablets.

The bioequivalence of a proprietary liquid dapsone preparation and commercially available dapsone tablets was studied. Twelve adult volunteers received dapsone doses with 8 oz of water one to two hours after their usual breakfast. Each subject received an initial 100-mg dose of a propylene glycol-based liquid preparation of dapsone and, two weeks later, a 100-mg dapsone tablet (both from Jacobus Pharmaceutical Company, Princeton, NJ). Blood samples were collected before and at intervals up to 96 hours after the administration of each dose. Serum dapsone concentrations were determined by high-performance liquid chromatography, and pharmacokinetic values were calculated by model-independent analysis. The area under the concentration-versus-time curve and the maximum serum concentration for the two formulations met the criteria for bioequivalence. Time to maximum serum concentration tended to be lower for the liquid, but not significantly. The liquid and tablet formulations of dapsone studied were found to be bioequivalent and may be used interchangeably.     

Relative bioavailability of ofloxacin tablets in comparison to oral solution

Summary

Single oral doses of solution and tablet preparations of 300?mg ofloxacin were given to 13 healthy male volunteers in an open, randomized crossover study. Concentrations of the unchanged drug were monitored at various times in serum and urine, over 28 hours and 48 hours, respectively. Each dose was followed by a 1-week washout period. Drug concentrations were measured both by a specific high pressure liquid chromatography (HPLC) method and a microbiological assay. A linear distribution independent regression analysis for method comparisons was calculated and good agreement between the two methods was found. Medians of maximum serum concentrations (C_max) of ofloxacin after oral solution and tablet form were 5.0?mg/l and 3.5?mg/l, respectively. The times to maximal serum concentration (t_max) were 0.5 hr and 1.0 hr, respectively. The lower C_max and later t_max after the tablet form were both statistically (p<0.05) different when compared to the corresponding values after the oral solution. However, the areas under the serum concentration-time curves (AUC_0-28), as also the urinary recoveries did not differ significantly, showing that only the speed of absorption, but not the bioavailability of the tablet is changed in comparison to the oral solution form. Long-lasting, clinically relevant urine concentrations of ofloxacin were observed after both forms until the last collecting fraction (36 to 48 hours after medication). General tolerability was good; no side-effects were reported.     

氧氟沙星滴眼剂临床疗效评价

目的：评价氧氟沙星滴眼剂的临床疗效及其安全性。方法：眼疾病病人验证组１２１例（男性６３例,１００只眼,女性５８例,８８只眼,年龄３０ａ±ｓ２１ａ）,用伊犁哈萨克自治州友谊医院研制的０．３％氧氟沙星滴眼剂。对照组３９例（男性１５例,２２只眼,女性２４例,３５只眼,年龄３５ａ±１０ａ）,用日本参天制药株式会社生产的０．３％氧氟沙星滴眼剂。每次均１滴（约０．２ｍＬ）,ｔｉｄ。治疗开始后ｄ４,ｄ７及ｄ１４复诊。结果：验证组细菌性眼疾病总显效率为７１．３％,对照组为３２％（Ｐ＜０．０１）。结论：伊犁哈萨克自治州友谊医院研制的氧氟沙星滴眼剂对细菌性眼疾有明显治疗作用。     

Bioavailability of lithium from lithium citrate syrup versus conventional lithium carbonate tablets.

The bioavailability of lithium citrate syrup was compared with that of regular lithium carbonate tablets in 18 healthy male human volunteers. Blood samples were collected up to 48 h after dosing. Lithium serum concentrations were determined by means of AAS. The absorption rate following oral administration of the syrup was greater (tmax 0.8 h) than following administration of regular tablets (tmax 1.4 h). Maximum lithium serum concentrations, however, were only about 10 per cent higher after syrup dosing and serum concentrations resulting from syrup and tablets were almost superimposable from 2 h after dosing. The terminal half-life of lithium was found to be 22 h after syrup as well as after tablet dosing. No side-effects were observed during the study. The bioavailability of lithium from syrup relative to tablets was found to be bioequivalent with respect to the maximum lithium serum concentration and the extent of drug absorption (AUC).