Bioavailability study of a 1200 mg miconazole nitrate vaginal ovule in healthy female adults.

This study was undertaken to determine the bioavailabilityof a 1200 mg miconazole nitrate vaginal ovule in 20 healthy premenopausal females following a single application (Day 1, Group 1) and two applications, 48 hours apart (Day 1 and Day 3, Group 2). In Dose Group 1 (n = 10), the mean Cmax of 10.7 ng/ml occurred at 18.4 hours. The average plasma miconazole concentration was calculated to be 5.7 ng/ml during the 4- to 96-hour time interval. In Dose Group 2 (n = 10), mean Cmax values were 10.8 ng/ml and 12.0 ng/ml and occurred at 18.4 hours (Day 1) and 16.0 hours (Day 3), respectively. Comparing AUC0-48 on Days 1 and 3 (338 vs. 408 ng x h/ml) indicated small accumulation of plasma miconazole, while AUC0-48 obtained from Dose Group 2, Day 1 was similar to that of Dose Group 1 (338 vs. 329 ng x h/ml, respectively). Plasma miconazole profiles were best described by a monoexponential equation with zero-order input. Pharmacokinetic simulations performed on the pooled data from two dose groups (n = 20) suggest a steady-state accumulation after five doses administered daily or three doses taken once every other day. Drug exposure was similar to that of the marketed formulation (MONISTAT 7 vaginal cream), applied once daily for 7 days and more than 100-fold less than that reported when given intravenously or orally.     

咪康唑栓与克霉唑阴道片单次给药治疗单纯性外阴阴道假丝酵母菌病比较

目的比较咪康唑栓与克霉唑阴道片单次给药治疗单纯性外阴阴道假丝酵母菌病(VVC)的疗效和安全性。方法单纯性VVC患者80例随机分为2组,各40例。试验组采用咪康唑栓1 200 mg阴道给药1次,对照组采用克霉唑阴道片500 mg阴道给药1次,分别于用药前、用药后d 7和用药后d 28～35进行妇科检查、临床症状体征评分、真菌学检查及不良反应评估。结果试验组1例患者失访,对照组2例患者失访,2组共完成有效病例77例。2组患者治疗前瘙痒、疼痛、充血水肿和分泌物增多的症状和体征组间均无显著差异(P>0.05);治疗后d 7及d 28～35与治疗前相比均有显著差异(P<0.05,P<0.01),组间相比均无显著差异(P>0.05)。治疗后d 7,试验组总有效率87%(34/39),对照组总有效率82%(31/38);治疗后d 28～35试验组总有效率95%(37/39),对照组总有效率92%(35/38),组间均无显著差异(P>0.05)。试验组1例患者出现外阴烧灼感,对照组1例患者出现外阴疼痛,症状较     

Comparative clinical trial of fenticonazole ovule (600 mg) versus clotrimazole vaginal tablet (500 mg) in the treatment of symptomatic vaginal candidiasis

A multi-centre, randomized, single-blind, parallel-group clinical trial was undertaken in 50 patients (26 fenticonazole, 24 clotrimazole) with symptomatic vaginal candidiasis to compare the antifungal efficacy and tolerability of single-dose intra-vaginal treatment with a fenticonazole ovule (600 mg) or a clotrimazole vaginal tablet (500 mg). Assessment was by laboratory mycological investigation and symptomatic assessments for a period of 3 weeks from the day of treatment. Of the 50 patients, 43 (23 fenticonazole, 20 clotrimazole) returned for assessment 1 week after drug administration and 32 (17 fenticonazole, 15 clotrimazole) were re-assessed 3 weeks after drug administration. Both treatments resulted in very similar and highly significant improvements in symptoms, associated with disappearance of detectable Candida in approximately 70% of patients. There were no significant differences between treatments and no appreciable incidence of relapse during the 3-week period of observation. At the end of this period, 10 (59%) of 17 fenticonazole patients were totally disease-free, as compared with 10 (67%) of 15 patients after clotrimazole treatment. The cure rate observed was somewhat less than that previously seen when intra-vaginal cream formulations of the same two drugs were given on a multiple-dose basis. Both drugs were very well tolerated, with no reports of appreciable local or systemic adverse reactions to either drug.     

制霉菌素片和达克宁(咪康唑)栓治疗复发性阴道念珠菌病疗效观察

目的观察制霉菌素片、达克宁（咪康唑）栓治疗复发性阴道念珠菌病（RVVC）的疗效。方法采用随机对照观察方法。对照组：达克宁（咪康唑）栓400mg;治疗组：制霉菌素片100万单位。均于每晚睡前清洗外阴后置入阴道内,7d为1疗程。于停药后第3天、下次月经干净后3～5d及停药2个月后观察疗效及复发情况。结果2组患者经治疗后症状积分均有明显下降（P〈0．01）,治愈率分别为74．0％（37／50）和93．88％（46／49）,差别有统计学意义（P〈0．05）。2组的总体疗效比较Ridit均值显示对照组疗效较差,治疗组疗效较好（R对照组〈R治疗组）。停药2个月后2组已治愈患者的复发率分别为16．22％（6／37）和13．04％（6／46）,差别无统计学意义（P〉0．05）。2组治疗期间来见明显的不良反应。结论制霉菌素阴道用药治疗RVVC安全有效,其疗效优于达克宁（咪康唑）栓。     

Double-blind, randomized trial of roxatidine 150 mg in the early evening versus bedtime administration in the short-term treatment of duodenal ulcer

Aim: To compare the efficacy and tolerability of early evening (19.00–21.00 hours) vs. bedtime (22.00–00.00 hours) oral administration of roxatidine 150 mg in the short-term treatment of active duodenal ulcer. Methods: The trial was randomized, double-blind and double-dummy, with parallel groups. A total of 276 patients were recruited and randomly assigned either to roxatidine in the early evening (n= 139) or roxatidine at bedtime (n= 137). Results: After 4 weeks, 78% of patients receiving roxatidine in the early evening and 74% of those treated at bedtime had achieved complete healing, as determined by per-protocol analysis. With intention-to-treat analysis the healing rates were 70.5% and 70.8%, respectively. After 8 weeks the healing rates in the early evening and bedtime treatment groups were 92% and 95% (per-protocol analysis) and 78% and 84% (intention-to-treat analysis). Both treatments proved effective in reducing the frequency and severity of daytime and nocturnal epigastric pain, as well as other ulcer-related symptoms. Conclusions: This study confirmed the healing and analgesic properties of roxatidine in duodenal ulcer disease. Early evening or bedtime dosing with roxatidine 150 mg resulted in similar 4- to 8-week rates of duodenal ulcer healing.     

盐酸特比萘芬阴道泡腾片治疗外阴阴道假丝酵母菌病71例

目的:观察盐酸特比萘芬阴道泡腾片治疗外阴阴道假丝酵母菌病(VVC)的有效性和安全性.方法:多中心随机法对照观察141例VVC患者,试验组(n=71)用盐酸特比萘芬阴道泡腾片50 mg·d-1,pd,对照组(n=70)用达克宁(硝酸咪康唑)栓,qd,两组疗程均为7 d.停药后7 d,进行组间和组内对比症状、体征、假丝酵母菌涂片和培养及生化指标的变化.结果:141例无生化指标异常改变和不良反应.ITT分析治疗后试验组和对照组两组假丝酵母菌涂片转阴率分别为95.77%(68/71)和98.57%(69/70)(P＞0.05).假丝酵母菌培养转阴率分别为95.77%(68/71)和94.29%(66/70)(P＞0.05).两组总体疗效有效率分别为94.37%(67/71)和90.00%(63/70).结论:盐酸特比萘芬阴道泡腾腾片用于VVC疗效确切,安全性好,剂型合理,用药方便.     

Safety and efficacy of antiemetics used to treat nausea and vomiting in pregnancy

The safety and efficacy of antiemetic drugs used in the treatment of nausea and vomiting during pregnancy are reviewed. Confirmation of the teratogenicity of drugs in humans is difficult; the risk can be estimated from results of cohort studies and case-control studies. The possible teratogenicity of Bendectin (doxylamine succinate and pyridoxine hydrochloride) was studied thoroughly; although the risk was minimal, the drug was withdrawn from the U.S. market. Whether phenothiazines are teratogenic has still not been conclusively determined. A large number of epidemiological studies have not shown meclizine to be teratogenic in humans. More information about metoclopramide is necessary before it can be safely recommended for use during pregnancy. The risks of using dimenhydrinate and diphenhydramine appear to be low. Pyridoxine is considered safe for use during pregnancy, but its efficacy in treating nausea and vomiting has not been determined. The relative efficacy of these agents has not been determined. The available data suggest that meclizine and dimenhydrinate are the antiemetics that present the lowest risk of teratogenicity; meclizine is the drug of first choice. Phenothiazines should be reserved for treating persistent vomiting that threatens the maternal nutritional status.     

Antipyretic efficacy and safety of a single intravenous administration of 15 mg/kg paracetamol versus 30 mg/kg propacetamol in children with acute fever due to infection

OBJECTIVES: An intravenous formulation of paracetamol and an intravenous formulation of propacetamol (prodrug of paracetamol) were compared in children with acute fever due to infection in order to determine the antipyretic efficacy and safety during the 6-hour period after administration. METHODS: A total of 67 patients aged 1 month to 12 years and with a rectal body temperature between 38.5 degrees C and 41 degrees C, were randomized to receive either intravenous paracetamol 15 mg/kg (n = 35) or propacetamol 30 mg/kg (n = 32) under double-blind conditions. RESULTS: The non-inferiority of intravenous paracetamol compared to propacetamol was demonstrated (non-inferiority margin = 0.5 degrees C) by the median body temperature reduction of 1.9 degrees C in the intravenous paracetamol group and the reduction of 2.05 degrees C in the propacetamol group. The difference in the incidence of local adverse events was statistically significant (p = 0.0134) with more local adverse events in the propacetamol group (9, 28.1%) than in the intravenous paracetamol group (2, 5.7%). CONCLUSION: This double-blind, randomized, clinical trial demonstrates the non-inferiority of a single administration of 15 mg/kg intravenous paracetamol in comparison to 30 mg/kg propacetamol in terms of body temperature reduction in children aged 1 month to 12 years with acute fever due to infection. It confirms the better local safety of intravenous paracetamol in comparison to propacetamol.     

特异性卵黄抗体抗念珠菌效果／安全性的双盲观察

目的评价特异性卵黄抗体（IgY）在治疗外阴阴道念珠菌病的临床疗效和安全性。方法采用随机双盲、安慰剂对照的方法,选择符合入选标准的100例患者随机使用IgY喷剂或安慰剂。结果两组各46例患者完成观察,两组患者的年龄、病期、症状均匹配。IgY喷剂组症状以及体征改善（t=-2．89,P〈0．05）、念珠菌清除率（Х^2=23．10,P〈0．001）、临床总有效率（Х^2=7．39．P〈0．05）显著优于安慰剂组,IgY喷剂组念珠菌清除率、临床总有效率、临床治愈率分别为71．74％、82．61％、21．74％。结论IgY喷剂有确切的抗阴道念珠菌活性及临床疗效,但由于临床治愈率较低,仍需进一步开发。     

初次妊娠早期无痛人流口服米索前列醇和阴道用药的疗效对比

目的:对比初次妊娠早期无痛人流口服米索前列醇和阴道用药的疗效.方法:选取78例初次妊娠早期无痛人流孕妇作为研究对象,均采取米非司酮结合米索前列醇进行终止妊娠,根据米索前列醇的给药途径进行分组;对照组39例,口服给药米索前列醇;观察组39例,阴道用药米索前列醇;对比两组孕妇的流产有效情况、产后2h流血量、产后24h流血量、流产时间、米索前列醇用量,根据不良反应发生情况,综合评价口服米索前列醇和阴道用药的疗效及安全性,并作对比分析.结果:观察组流产有效率为100.0％,对照组流产有效率为94.87％;两组数据具有显著差异(P＜0.05);观察组产后2h流血量及米索前列醇用量均显著少于对照组,流产时间显著短于对照组;两组数据具有显著差异(P＜0.05);两组孕妇的药物不良反应以胃肠道反应为主,观察组恶心、呕吐、腹泻及发热寒战的发生数显著少于对照组;两组数据具有显著差异(P＜0.05).结论:米索前列醇治疗初次妊娠早期无痛人流,阴道用药与口服用药对比,发挥更好的流产效果,米索前列醇用量少、不良反应少及安全性高,可作为米索前列醇用于药物流产的理想给药途径之一.     

Analgesic efficacy of acetaminophen 1000 mg, acetaminophen 2000 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg versus placebo in acute postoperative pain.

Acetaminophen (APAP) 1000 mg, APAP 2000 mg, the combination of APAP 1000 mg plus codeine phosphate 60 mg (APAPCOD), and placebo (PBO) were compared in a 6-hour, randomized, single-dose, double-blind, parallel-group analgesic trial. All active treatments were statistically superior (p less than 0.05) to placebo for 4 hours after medication with respect to pain intensity (PI) and pain intensity difference (PID), and up to 3 hours regarding pain relief (PAR). The combination scored better than all other treatments on the summary analgesic efficacy measures sum PI (SUMPI), sum PID (SPID), and total PAR (TOTPAR). The combination was statistically superior to APAP 1000 mg on SUMPI, TOTPAR and maximum PAR (MAXPAR). Acetaminophen 2000 mg showed marginal numerical superiority over 1000 mg for SUMPI, but was not statistically superior for any summary efficacy measure. The 2000-mg dose was numerically inferior to APAPCOD for every summary efficacy measure and statistically inferior regarding SPID and MAXPAR. We concluded that codeine 60 mg added to acetaminophen 1000 mg offers analgesic advantages, and acetaminophen reaches an analgesic ceiling effect at 1000 mg using the dental pain model.     

Safety and efficacy of lifibrol upon four-week administration to patients with primary hypercholesterolaemia

The efficacy and safety of lifibrol, a novel cholesterol-lowering drug, was investigated in a double-blind clinical study in 168 patients with primary hypercholesterolaemia. Placebo and four lifibrol dose groups (150, 300, 450 and 600 mg/day) were tested over a period of 4 weeks.The mean LDL-cholesterol changes were 5.7%, –11.1%, –27.7%, –34.5% and –35.0%, respectively, after 4 weeks of treatment. No major changes in HDL-cholesterol were seen after this period. With the present study design, a decrease in triglycerides (–28%) was significant in the highest dosage group only. Additionally, it was shown that further independent risk factors for coronary heart disease were favourably influenced. Fibrinogen decreased in all dosage groups with a maximal mean value of 18% and a tendency toward reduction in lipoprotein (a) was observed in patients with high baseline levels (>30 mg·dl^–1).Lifibrol was generally well tolerated in all dosage groups and no serious adverse events were reported. Laboratory parameters did not show any clinically relevant alterations.P. Schwandt is representing the 22 medical centres of the Lifibrol Study Group     

The influence of food on the pharmacokinetics of CGP 6140 (amocarzine) after oral administration of a 1200 mg single dose to patients with onchocerciasis.

Eleven male patients from Mali with Onchocerca volvulus infections received in random order a 1200 mg single oral dose of CGP 6140 after an overnight fast and after food intake. The concentrations of CGP 6140 and of its N-oxide metabolite, CGP 13231, were measured in plasma and urine. Mean (+/- s.d.) AUC CGP 6140 values were 67.0 +/- 10.8 mumol l-1 h in fed and 22.0 +/- 17.2 mumol l-1 h in fasting patients. The mean maximum concentrations (Cmax) in plasma +/- s.d. were 12.7 +/- 2.8 mumol l-1 in fed and 4.7 +/- 4.1 mumol l-1 in fasting patients. The median time to Cmax was 3 h in fed and 2 h in fasting patients. Mean (+/- s.d.) AUC of the N-oxide metabolite was 59.9 +/- 10.7 mumol l-1 h in fed and 23.4 +/- 16.2 mumol l-1 h in fasting patients. The urinary recovery was less than 0.5% of dose for CGP 6140 in both fed and fasting conditions. It was 30.1 +/- 11.5 and 11.4 +/- 8.0% of the dose for the N-oxide metabolite in fed and fasting conditions, respectively. Variability in plasma concentrations and urinary recovery of CGP 6140 and of the N-oxide metabolite was greater in fasted patients. The low solubility of CGP 6140 in aqueous solutions at neutral pH and its higher solubility at acidic pH might explain the increase in bioavailability after food intake. The administration of CGP 6140 after food intake is therefore recommended for an optimal systemic effect.     

A single-dose study of the efficacy and safety of FS 205-397 (250 mg or 500 mg) versus aspirin and placebo in the treatment of postsurgery dental pain

The efficacy and safety of two dose levels of FS 205-397 (either 250 or 500 mg) were compared with the efficacy and safety of aspirin 650 mg and placebo in a 6-hour, single-dose, double-blind study in 161 patients who had undergone extraction of third molars. Each of the doses of FS 205-397, as well as aspirin, produced analgesia. However, the analgesic effects of both the 500 mg dose of FS 205-397 and aspirin were at times significantly better and more prolonged than those produced by the lower dose of FS 205-397. On the other hand, both doses of FS 205-397 had a significantly faster onset of action than aspirin. Side effects, reported by 17% of the 161 patients, did not differ significantly among the four treatment groups with respect to frequency, type, or severity. The most commonly reported side effects were nausea (7%) and drowsiness (6%). The results indicated that FS 205-397, administered in single doses of either 500 or 250 mg, is a safe and effective analgesic for the relief of pain following dental surgery, and may offer particular advantages in terms of onset of effects.     

A new tool to enhance the efficacy of chemoembolization to treat primary and metastatic hepatic tumors

This editorial focuses primarily on a paper that presented the clinical applications of a new material, named DC Bead embolic drug-eluting bead (DEB), which is used to modulate the blood flow in conjunction with chemotherapy in primary and metastatic hepatic tumors. DEB appears to have several advantages over alternative embolization agents, not least of which is its effective capacity of drug diffusion in tumors, thereby making it suitable for ideal treatments.     

A new tool to enhance the efficacy of chemoembolization to treat primary and metastatic hepatic tumors

This editorial focuses primarily on a paper that presented the clinical applications of a new material, named DC Bead embolic drug-eluting bead (DEB), which is used to modulate the blood flow in conjunction with chemotherapy in primary and metastatic hepatic tumors. DEB appears to have several advantages over alternative embolization agents, not least of which is its effective capacity of drug diffusion in tumors, thereby making it suitable for ideal treatments.     

Comparison of the pharmacodynamics and pharmacokinetics of pantoprazole (40 mg) as compared to omeprazole MUPS (20 mg) after repeated oral dose administration

The effects on intragastric p11 and gastrin secretion of once daily pantoprazole (40 mg) and a new formulation omeprazole (20 mg) in a Multiple Unit Pellet System (MUPS) were investigated during two treatment periods of 7 days each in a randomized crossover study with 16 healthy Helicobacter pylori-negative male volunteers. Intragastric pH was measured using continuous 24 hour pH-metry on days 1 and 7. The results were compared to the baseline curves obtained before each treatment period. On day 1, pantoprazole raised the intragastric pH significantly higher and more quickly than omeprazole MUPS (pH median 1.9 vs. 1.6, baseline pH 1.4). After 7 days, the 24 h gastric pH medians were still in favor of pantoprazole (pH 3.0 vs. 2.8). With respect to the basal gastrin concentration, both treatments resulted in similar increases. For pantoprazole, no differences were observed in AUC and Cmax after single and repeated dosing. However, the new omeprazole MUPS formulation still showed the well-known effect of initial low bioavailability increasing after repeated dosing. Pantoprazole and omeprazole were well tolerated. There seems to be no advantage in the new omeprazole formulation compared with the conventional capsule with regard to bioavailability and increase in intragastric pH. The results of this study confirm former results in which pantoprazole (40 mg) was shown to be significantly superior to omeprazole (20 mg) in elevating intragastric pH.     

Comparison of the pharmacokinetics of miconazole after administration via a bioadhesive slow release tablet and an oral gel to healthy male and female subjects

AIMS: The aim of this study was to compare salivary miconazole pharmacokinetics following once daily application of bioadhesive tablets (50 or 100 mg), vs the current treatment with a gel (3 times a day, 375 mg day(-1)). METHODS: A three way cross over study was carried out in 18 healthy subjects (nine males, nine females) with a 1 week washout period between each treatment. Plasma and salivary pharmacokinetics of miconazole were assessed over a 24-h period. RESULTS: In all subjects the tablets gave higher and more prolonged salivary miconazole concentrations than the gel. Thus salivary miconazole AUC(0,24 h) was 37.2 times greater for the 100 mg tablet (90% confidence interval [CI] 22.9, 60.5) and 18.9 times greater for the 50 mg tablet (CI 11.7, 30.6) compared with the gel. Similarly, Cmax was 17.2 times greater (CI 11.8, 25.2) and 7.8 times greater (CI 5.3, 11.4) for the 100 mg tablet and 50 mg tablet, respectively. Comparison of the 100 mg and 50 mg tablets gave ratios of 2.2 and 2.0 for Cmax and AUC(0,24 h), respectively (CI 1.5, 3.2 and 1.2, 3.2). The mean time that salivary miconazole concentrations were above 0.4 micro g ml(-1) (the concentration reached 3 h after application of the oral gel according to published data) or above 1.0 microg ml(-1) (the MIC of some Candida species) was greater for both bioadhesive tablets than for the oral gel (10-14 h vs 1.5 h and 7 h vs 0.6 h). Only 19 plasma samples from eight subjects had concentrations of miconazole above 0.4 micro g ml(-1). Ten of these were taken from five subjects after administration of the gel and nine from three subjects after administration of the tablets. CONCLUSIONS: These data strongly support the further development of miconazole bioadhesive tablets as a sustained release formulation leading to improved antifungal exposure in the buccal cavity. A single daily application should improve compliance, whereas the low systemic absorption of miconazole will alleviate concerns regarding drug interactions and adverse effects.