Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C

Background and Aim: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. Methods: A total of 7715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2515 (32.6%) patients. Of these 2515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. Results: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4–9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow‐up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P = 0.002). Conclusions: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.     

Ketoprofen Versus Paracetamol in the Treatment of Acute Migraine

The efficacy and safety of ketoprofen and paracetamol were compared for the treatment of acute migraine in a randomized, double-blind study of 64 patients. Thirty-four patients received ketoprofen 100 mg intramuscularly, and 30 patients received paracetamol 500 mg intramuscularly. Partial or complete relief of pain and other symptoms was achieved 15 to 20 minutes after administration in the ketoprofen group and within 35 minutes in the paracetamol group. Complete relief of pain was achieved within 30 to 40 minutes after ketoprofen in 28 patients (82.5%) compared to 5 patients (17.5%) in the paracetamol group. Six of the patients treated with ketoprofen needed a second dose for complete relief of pain during the 4-hour follow-up period. Side effects were rare and minimal. Our findings suggest that ketoprofen produced statistically significant benefit in the treatment of acute migraine.     

马来酸罗格列酮胃漂浮型缓释片的研究

目的：根据流体动力学平衡控释原理（HBS）研制了马来酸罗列酮胃漂浮型缓释片。方法；以体外释放度和漂浮情况为筛选指标，采用单因素考察和正交试验设计相结合， 对胃漂浮缓释片的处方、制备工艺及体外释放条件进行优化筛选；采用γ闪烁照相技术对优化处方的内漂浮情况进行胃内动态观察。结果：马来酸罗格列酮胃漂浮缓释片在释放介质中迅速起漂，持漂时间超过12h,12h达最大累积释放；初步确定在胃内滞留时间达3h以上。结论：优化处方的释放过程符合Higuchi方程，释放机制为异常扩散；胃漂浮片在胃滞时间明显长于普通片。     

In Vitro and in Vivo Evaluation of Whole and Half Tablets of Sustained-Release Adinazolam Mesylate

The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.     

Effect of buffering on pharmacokinetics of ketoprofen enantiomers in man

Aims Concomitant administration of magnesium hydroxide may affect the rate or extent of absorption of non-steroidal anti-inflammatory drugs. In order to find out whether or not buffering modifies the pharmacokinetics of ketoprofen, plasma concentration-time courses resulting from oral administration of unbuffered formulations were compared with those of buffered formulations.
Methods Two groups of 12 healthy and young male subjects were included in two randomized cross-over studies and received single oral doses of ketoprofen 12.5 or 25  mg, respectively, given as tablets which were either unbuffered or buffered with magnesium hydroxide/citrate. Ketoprofen enantiomers in plasma were determined by h.p.l.c. up to 24  h post-dose.
Results Maximum plasma concentrations ( C _max ) of both the (R)- and (S)-enantiomer, observed after administration of the buffered formulations (12.5 and 25  mg), were higher compared with the unbuffered tablets by about 50–80%. The area under concentration-time data (AUC) was unaffected, and, hence, C _max/AUC was increased by buffering. Time to C _max ( t _max ) and mean residence time (MRT) tended to be or was shortened by buffering.
Conclusions It is concluded that buffering of two ketoprofen formulations with magnesium hydroxide/citrate enhanced the concentration maximum by increasing the rate of absorption and leaving AUC unaffected.     

Formulation and in Vitro-in Vivo Evaluation of Sustained-Release Lithium Carbonate Tablets

The release of lithium carbonate incorporated into polymethylmethacrylate, poly vinyl chloride, hy-drogenated vegetable oil, and carbomer matrix tablets was studied in vitro. The formulation containing 10% carbomer showed a sustained-release profile comparable to that of a standard, commercially available, sustained-release preparation containing 400 mg lithium carbonate embedded in a composite material. In vivo the newly formulated and standard sustained-release lithium carbonate tablets were compared to an oral solution and conventional lithium carbonate tablets in 12 healthy subjects. These crossover studies showed that the sustained-release tablets produced a flatter serum concentration curve than the oral solution and conventional tablet, without loss of total bioavailability.     

萘普生缓释胶囊的药代动力学和生物利用度研究

目的 通过健康受试者的双交叉试验比较萘普生缓释胶囊与普通片的药物动力学和生物利用度。方法１０位健康受试者一次服用这两种制剂５００ｍｇ，在稳态试验中８位受试者接受两种制剂５天，缓释胶囊５００ｍｇ每天一次，普通片每天两次，每次２５０ｍｇ。血药浓度用ＨＰＬＣ方法测定。结果 一次服药试验证明该缓释胶囊血药浓度上升缓慢，浓度变化平稳，Ｇｍａｘ为８５．９μｇ／ｍｌ，Ｔｐｅａｋ为６．０ｈ，而普通片的Ｃｍａｘ为１４０．４μｇ／ｍｌ，Ｔｐｅａｋ为３．２ｈ，两种制剂的生物利用度相当，缓释胶囊与普通片生物等效。通过８位健康受试者交叉连续服用萘普生缓释胶囊与普通片的稳态药代动力学研究表明，到第３天给药后已达到稳态，由第５天给药后的血药浓度测定数据计算其主要的稳态药代动力学参数，缓释胶囊的峰浓度（Ｃｍａｘ）、峰谷比和波动度（ＤＦ）明显低于普通片，这些参数分别为７３，１μｇ／ｍｌ、１．４８和３７．７ｏ；而普通片的上述参数分别为 １００．８μｇ／ｍｌ、２．５１和７８．２％。结论 奈普生缓释胶囊具有缓释作用，能较好维持血药治疗浓度。     

吗啡抑制大鼠多觉型伤害性感受器持续放电

作利用复合致痛剂引起大鼠尾部皮肤多觉型伤害性感受器（ＰＭＮ）持续性放电模型，经股静脉注入吗啡（４ｍｇ／ｋｇ），显抑制ＰＭＮ持续性放电。吗啡抑制ＰＭＮ放电５０％的潜伏期为１０±４．５ｍｉｎ，抑制时程超过３０ｍｉｎ。纳络酮１ｍｇ／ｍｇ ｉｖ，可翻转吗啡的抑制作用。在慢性吗啡耐受大鼠，吗啡几乎失去其抑制作用。吗啡引起的ＰＭＮ放电数变化不呈一致关系。小剂量吗啡（１ｍｇ／ｋｇ）注入支配感受野皮肢的尾动脉     

A theophylline dosage regimen which reduces round-the-clock variations in plasma concentrations resulting from diurnal pharmacokinetic variation

Summary Slower drug absorption at night can leave residual drug from an evening dose of a sustained-release product remaining to be absorbed at the time of the next morning's dose, thereby giving higher plasma concentrations of the drug during the day than the night.When a capsule product releasing theophylline over 12 h after a morning dose was given repetitively at 8 a.m. and 8 p.m. for 4 days, daytime plasma concentrations from 4 h to 8 h after the dose were about 40% greater than corresponding night-time concentrations, and the mean steady-state concentration during the night-time interval was only 81% of that during the daytime interval.Altering the regimen to one capsule at 12 noon and one at 10 p.m. eliminated all significant differences between a.m. and corresponding p.m. plasma concentrations of theophylline and between the mean steady-state concentrations for each of the interdose intervals within a day.     

控制性肺膨胀在食管癌术后应用的临床对比研究

目的　观察在食管癌术后应用控制性肺膨胀防止急性呼吸衰竭的疗效。方法　随机设立应用控制性肺膨胀组 4 3例和对照组 33例 ,年龄和手术时间等无显著差异。观察撤离呼吸机时间。撤机后 1 2、2 4h的呼吸频率、心率、血氧饱和度和氧分压。结果　 (1 )应用控制性肺膨胀后 ,撤机时间由 (1 0 4± 1 5 )min缩短到 (87± 1 3)min。 (2 )撤机后 1 2h ,控制性肺膨胀组血氧饱和度和氧分压异常的患者率分别由 30 .30 %下降到 6 .98% ,2 4 .2 4 %下降到 6 .98%。 (3)撤机后 2 4h ,血氧饱和度异常的患者率由1 8.1 8%下降到 2 .33%。结论　食管癌术后应用控制性肺膨胀能有效防止急性呼吸衰竭的发生。