Understanding peroral absorption: regulatory aspects and contemporary approaches to tackling solubility and permeability hurdles

Oral drug absorption is a process influenced by the physicochemical and biopharmaceutical properties of the drug and its inter-relationship with the gastrointestinal tract. Drug solubility, dissolution and permeability across intestinal barrier are the key parameters controlling absorption. This review provides an overview of the factors that affect drug absorption and the classification of a drug on the basis of solubility and permeability. The biopharmaceutical classification system (BCS) was introduced in early 90׳s and is a regulatory tool used to predict bioavailability problems associated with a new entity, thereby helping in the development of a drug product. Strategies to combat solubility and permeability issues are also discussed.     

Strawberry consumption alleviates doxorubicin-induced toxicity by suppressing oxidative stress

Doxorubicin (Dox), one of the most used chemotherapeutic agents, is known to generate oxidative stress and block DNA synthesis, which result in severe dose-limiting toxicity. A strategy to protect against Dox toxic effects could be to use dietary antioxidants of which fruits and vegetable are a rich source. In this context, strawberry consumption is associated with the maintenance of good health and the prevention of several diseases, thanks to the antioxidant capacities of its bioactive compounds. The aim of the present study was to evaluate the protective effects of strawberry consumption against oxidative stress induced by Dox in rats. Animals were fed with strawberry enriched diet (15% of the total calories) for two months and Dox (10 mg/kg; i.p.) was injected at the end of the experimental period. Strawberry consumption significantly inhibited ROS production and oxidative damage biomarkers accumulation in plasma and liver tissue and alleviated histopathological changes in rat livers treated with Dox. The reduction of antioxidant enzyme activities was significantly mitigated after strawberry consumption. In addition, strawberry enriched diet ameliorated liver mitochondrial antioxidant levels and functionality. In conclusion, strawberry intake protects against Dox-induced toxicity, at plasma, liver and mitochondrial levels thanks to its high contents of bioactive compounds.     

The polyphenol-rich baobab fruit (Adansonia digitata L.) reduces starch digestion and glycemic response in humans

The baobab fruit (Adansonia digitata L.) is found throughout regions of Africa and is becoming increasingly recognized for its high nutrient and polyphenol content. Polyphenols have been beneficial for their effects on reducing the glycemic response (GR) and for improving various other metabolic parameters. Based on previous research, it was hypothesized that the baobab fruit extract would reduce starch digestion in vitro and would show potential for reducing the GR and for increasing satiety and diet-induced thermogenesis in humans. Six extracts of baobab from 6 different locations in Africa were measured for their antioxidant and polyphenol content using the ferric ion–reducing antioxidant power and the Folin-Ciocalteu methods, respectively. Baobab extract was baked into white bread at different doses to determine the optimal dose for reducing starch breakdown and sugar release from white bread after an in vitro digestion procedure. In vivo, baobab extract was consumed in solution at both a low-dose (18.5 g) and a high-dose (37 g) aqueous drink in 250 mL of water along with white bread, and resulting GR, satiety, and postprandial energy expenditure were measured. All extracts in this study were shown to be good sources of polyphenols. Baobab fruit extract added to white bread at 1.88 % significantly (P < .05) reduced rapidly digestible starch from white bread samples. In vivo, the baobab fruit extract at both low and high doses significantly (P < .05) reduced GR, although there was no significant effect on satiety or on energy expenditure.     

调和阴阳针法联合vitB_1治疗周围性面瘫39例临床观察

[目的]观察调和阴阳针法联合vitB1治疗周围性面瘫疗效。[方法]使用前瞻性设计方法,对39例住院患者使用1调和阴阳针法(百会及双侧风池、合谷、足三里、太冲),百会毫针斜刺、余穴直刺,刺入0.5~1.5寸,行平补平泻手法,患者稍有针感为宜,留针30min,1次/d。2vitB1 10mg,3次/d。连续治疗7d为1疗程。观测临床症状、不良反应。连续治疗4疗程,判定疗效。[结果]痊愈28例,显效7例,有效4例,无效0例,总显效率89.84%。[结论]调和阴阳针法联合vitB1治疗周围性面瘫,疗效满意,无副作用,值得推广。     

Inhibition of the in vitro growth of Plasmodium falciparum by D vitamins and vitamin D-3 derivatives

D vitamins are effective inhibitors of the in vitro intraerythrocytic growth of Plasmodium falciparum. Disappearance of the parasitemia was observed after 48 h contact between infected cells and 5 x 10(-6) M 1 alpha-hydroxycholecalciferol, 5 x 10(-5) M 25-hydroxycholecalciferol (25-OH-D-3), 1 alpha, 25-dihydroxycholecalciferol or 2.5 x 10(-4) vitamin D-2 and D-3. A 48 h pretreatment of healthy erythrocytes with 5 x 10(-5) M 25-OH-D-3 did not change their susceptibility to invasion by the parasite and their ability to support the growth of P. falciparum. Ionomycin, a calcium ionophore, and EGTA prevented parasite development at concentrations greater than 2 x 10(-7) M and 4 x 10(-4) M, respectively, but did not antagonize the inhibitory activity of 25-OH-D-3. Addition of 25-OH-D-3 for 12 or 24 h duration to synchronized cultures, showed that the drug had a schizonticidal action, but was without effect when parasites were in the ring form.     

Methiocarb-induced oxidative damage following subacute exposure and the protective effects of vitamin E and taurine in rats

Methiocarb, is used worldwide in agriculture and health programs. Besides its advantages in the agriculture, it causes several toxic effects. In this study, we aimed to investigate subacute effects of methiocarb on lipid peroxidation, reduced glutathione (GSH), antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) and histopathological changes in rat tissues. Moreover, we examined the possible protective effects of vitamin E and taurine on methiocarb-induced oxidative damage in rat tissues. Rats were randomly divided into six groups as follows; I-control group; II-methiocarb group; III-vitamin E group; IV-vitamin E + methiocarb group; V-taurine group and VI-taurine + methiocarb group. Methiocarb significantly increased lipid peroxidation in liver and kidney when compared to control groups. Levels of GSH and activities of SOD, CAT and GSH-Px were found to be decreased, while GSH-Rd remained unchanged in rat liver and kidney treated with methiocarb. Pretreatment of vitamin E and taurine resulted in a significant decrease on lipid peroxidation, alleviating effects on GSH and antioxidant enzymes. The degenerative histological changes were less in liver than kidney of rats treated with methiocarb. Pretreatment of vitamin E and taurine showed a protective effect on the histological changes in kidney comparing to the liver of rats treated with methiocarb.     

抗氧化剂对小鼠腹水型肝癌(H_(22))血清LPO的影响

本文在观测荷癌小鼠过氧化脂质(LPO)水平动态变化的基础上,观察了几种抗氧化剂对该动物血清LPO水平的影响。结果发现,小鼠接种H_(22)腹水癌细胞后,血清LPO逐日增高,至第6天达最高峰。硒(Na_2SeO_3lmg/kg)和维生素E(5mg/kg)对宿主血清LPO均有明显的降低作用。小剂量维生素E(1mg/kg)或较大剂量维生素C(300mg/kg)单独使用时,未见对LPO值有显著影响,后两剂量维生素与小剂量的硒3种抗氧化剂,任何两种合并使用时均能明显降低血清LPO水平;3种合用时,作用最显著。这几种抗氧化剂对小鼠腹水型肝癌细胞的增殖具有明显抑制作用。     

鱼肝油乳剂中维生素D_3的高效液相色谱测定法

用高效液相色谱法测定含VD_3 30～60IU/g的鱼肝油乳剂中的VD_3含量。取样品10g皂化2.25h,用乙醚萃取。提取物通过反相色谱柱,收集含 VD_3的流出液,再用正相色谱柱定量,样品峰值与在皂化温度下达到平衡时 VD_3所应占百分比算得的标准品 VD_3峰值相比较,回收率94.9～104.6%,c.v.3.15%(n=12)。     

老年骨质疏松患者服用钙加维生素D后骨密度及生化指标的改变

目的了解补充钙和维生素D对骨丢失和骨转换的影响。方法对31例门诊原发性骨质疏松症和骨量减少患每日服用1片碳酸钙和维生素D复合剂(每片含元素钙600mg和维生素D125IU),连服6个月。治疗前后检测腰椎骨密度(BMD)、骨矿含量(BMC)及骨转换生化指标。结果碳酸钙和维生素D复合剂每日1片能明显改善骨质疏松引起的腰背疼和腿痛性痉挛,有明显疗效。可以维持腰椎骨密度,明显增加男性腰椎骨矿含量( 2．7％),与治疗前比较,明显提高血清250HD( 13．8％)和BGP(％29．5％),减少尿HOP／Cr比值(-17．5％)。结论老年人每天1片碳酸钙和维生素D复合剂对防止骨丢失,改善维生素D的营养状态,促进骨形成和抑制骨吸收有一定作用。