Bioequivalence and Pharmacokinetic Profiles of Generic and Branded Obeticholic Acid in Healthy Chinese Subjects Under Fasting and Fed Conditions.

OBJECTIVES: This study was conducted to evaluate the bioequivalence (BE) of a generic form of obeticholic acid (OCA) and OcalivaTM under fasting and fed conditions and to determine the effects of food on the pharmacokinetic (PK) profiles of OCA in healthy Chinese subjects. METHODS: A randomized, single-dose, three-sequence, three-period, partial replicated crossover study was conducted with a 21-day washout interval between periods under fasting (n=48) and fed (n=48) conditions. Blood samples for OCA and its metabolites Glyco-OCA and Tauro-OCA were collected up to 168 hours after administration in each period. PK parameters were calculated using the non-compartmental method. Geometric mean ratios for PK parameters of the test to reference drug under fasting and fed conditions and their 90% confidence intervals were estimated. Safety evaluations were carried out all through the study. RESULTS: A total of 91 subjects completed the study with 45 in a fasted state and 46 receiving a high-fat diet. There were no serious or unexpected drug-related adverse events occurring during the study. There was no significant difference in the main PK parameters of the two preparations, irrespective of the fasting or fed conditions. Under fasting and fed conditions, the SWR of lnCmax, lnAUC0-t and lnAUC0-∞ were 0.445, 0.370, 0.448, 0.340, 0.168, and 0.180, respectively. Thus, the average BE or the reference-scaled average BE was used to verify that the two preparations were bioequivalent under fasting and fed conditions. Compared with the fasting state, the AUC0-t of the test drug, the AUC0-t, and AUC0-∞ of the reference drug were higher in the fed state. CONCLUSION: The test drug and the reference drug were BE and well tolerated in Chinese healthy subjects under both fasting and fed conditions. Food-intake may cause a significant difference in the main PK parameters of the two preparations.

Time-dependent stress evidence in dynamic allocation of physiological metabolism of Nilaparvata lugens in response to elevated CO2.

To assess the time-dependent stress evidence in dynamic allocation of physiological metabolism of Nilaparvata lugens nymphs in response to elevated CO2, we measured the time-dependent allocation of nutrient compositions and physiological metabolism in the bodies of N. lugens at 1h, 4h and 12h under elevated CO2. Elevated CO2 significantly increased the contents of nutrient compositions (protein, glucose and total amino acids) and catalase (CAT) enzyme activity in the body of N. lugens at 12h relative to 1h and 4h (P < 0.05). Significantly higher genes expression levels of acetylcholinesterase (AChE), heat shock protein (HSP70) and vitellogenin gene (vg) were observed in the body of N. lugens compared with those in ambient CO2 at 4h (P < 0.05). These results showed that there was an instantaneous reaction of N. lugens nymphs to elevated CO2, which indicated N. lugens may enhance stress defense response to future increasing CO2 levels.

[Assessment of health education against echinococcosis in Tibetan region of Sichuan Province, China].

OBJECTIVE: To find an effective strategy of implementing health education in Tibetan Regions so as to make echinococcosis control sustainable at a large scale. METHODS: During July to November of 2008, surveys were conducted on health education requirements among various populations in the form of questionnaire and group discussion in endemic areas of echinococcosis in three counties of the Ganzi Tibetan Autonomous Prefecture, Sichuan. Based on the obtained results, health education materials suitable for different populations were designed. The materials were applied for conducting health education in field at Tagong Township, Kangding of Ganzi in October, 2009. By the survey in May, 2010, the improved effect on knowledge and behavior change was compared before and after (6 months later) health education in order to assess the usefulness of these materials. Simultaneously, Xinduqiao Township of Kangding was selected as control. This town is neighboring to the study area with similar natural and demographic conditions, in which no health education activities related to the study was implemented. RESULTS: Various populations showed their interested requirements for health education materials and ways. Based on the information collected, a series of materials were designed and applied for health education activities in field. The results indicated that, compared with the data before health education, improvement of the knowledge and behaviors against echinococcosis among students and local residents showed significant increase (P < 0.05), but only one knowledge point about the importance of washing hands before meal among students showed no significant difference (P > 0.05) in spite of the rates increasing from 88.6% (78/88) before health education to 95.5% (84/88) after education. The local officers and monks also showed to some extent improvement on behavior manners. The rate of correct treatment of livestock viscera increased from 37.1% (13/35) and 30.3% (10/33) before the education to 82.9% (29/35) and 78.8% (26/33) (P < 0.01), while the rate of not feeding stray dogs among monks was 6.4% (3/47) before and 10.6% (5/47) (P > 0.05) after the education. The knowledge-increasing and behavior-improving rates on playing dogs among the students, residents and monks increased by 182% and 193%, 42.8% and 54.3%, 6.4% and 14.9%, respectively. There was no considerable change in the control township. CONCLUSION: The materials designed for health education are acceptable by most populations. The improvement rate of knowledge and behaviors is considerable among the groups. Use of the materials receives expected effect on health education and health promotion.

Determination of 17 pyrethroid residues in troublesome matrices by gas chromatography/mass spectrometry with negative chemical ionization.

An analytical method with the technique of QuEChERS (quick, easy, cheap, effective, rugged and safe) and gas chromatography (GC)/mass spectrometry (MS) in negative chemical ionization (NCI) has been developed for the determination of 17 pyrethroid pesticide residues in troublesome matrices, including garlic, onion, spring onion and chili. Pyrethroid residues were extracted with acidified acetonitrile saturated by hexane. After a modified QuEChERS clean-up step, the extract was analyzed by GC-NCI/MS in selected ion monitoring (SIM) mode. An isotope internal standard of trans-cypermethrin-D(6) was employed for quantitation. Chromatograms of pyrethroids obtained in all these matrices were relatively clean and without obvious interference. The limits of detection (LODs) ranged from 0.02 to 6 µg kg(-1) and recovery yields were from 54.0% to 129.8% at three spiked levels (20, 40 and 60 µg kg(-1) for chili, and 10, 20 and 30 µg kg(-1) for others) in four different matrices depending on the compounds determined. The relative standard deviations (RSDs) were all below 14%. Isomerization enhancement of pyrethroids in chili extract was observed and preliminarily explained, especially for acrinathrin and deltamethrin.

Safety and quality assessment of 175 illegal sexual enhancement products seized in red-light districts in Singapore.

BACKGROUND: In recent years, there has been increasing interest in the use of herbs and supplements as an alternative to drugs used for the treatment of erectile dysfunction, in order to enhance sexual performance. Over the years, adverse events associated with the consumption of natural health products for sexual enhancement and the treatment of erectile dysfunction have been reported. OBJECTIVE: The objective of this work was to assess the safety and quality of 175 sexual enhancement health products seized from makeshift stalls in red-light districts of Singapore. METHOD: Seven raids were conducted by the Health Sciences Authority, Singapore, in two red-light districts in February and March 2008. 175 sexual enhancement health products seized from makeshift stalls were extracted with methanol and screened for Western drug adulterants using high performance liquid chromatography and gas chromatography-mass spectrometry. The labels and claims of the products were also evaluated. RESULTS: Of the 175 products evaluated, 134 (77%) were found to be adulterated with Western drugs or their analogues. Most of these 134 samples (123 [92%]) were found to be adulterated with sildenafil. The extent of adulteration of these illegal health products with Western drugs, including synthetic phosphodiesterase type 5 enzyme (PDE-5) inhibitors, and the risks of consuming such illegal sexual enhancement products are discussed in this study. Because of the scope of the raids, sildenafil was the most common adulterant found. In addition, some products were found to contain high contents of sildenafil (>100 mg) and high contents of the antidiabetic drug, glibenclamide (glyburide). The resultant severe hypoglycaemia has led to ten fatalities. CONCLUSION: The presence of Western drug adulterants and their analogues in illegal sexual enhancement products seized from red-light districts in Singapore, and their often misleading labels and claims, put the health of consumers at risk. To safeguard public health, greater public awareness of the danger of consuming such illegal products and the lack of quality control of these illegal sexual enhancement health products is important.