饮水量对口服药物生物利用度的影响

口服给药的生物利用度受许多因素影响。主要有:药物的理化性质、制剂类型和质量,各种食物对药物吸收的影响、肝脏的首过作用,以及不同疾病、不同年龄等等.     

提高难溶性口服药物生物利用度方法研究

目的探讨提高难溶性口服药物生物利用度的方法。方法综述了影响药物吸收的因素以及改善难溶性药物吸收的方法。结果药物的吸收是影响药物生物利用度的重要因素,其吸收过程与药物因素、剂型因素、生理因素等有密切关系。结论随着药学领域中新技术、新材料的发展,难溶性药物通过口服给药也可获得较好的吸收和生物利用度。     

食物对口服药物生物利用度的影响

本文综述了在空腹和食物存在条件下,药物生物利用度的变化及其原因.由于食物与口服给药的关系是密切的、所以临床用药工作中应考虑食物对药物吸收的影响.     

Merrion公司利用GIPET平台技术提高口服药物生物利用度

爱尔兰Merrion制药公司最近宣布，已与一家全球10强制药企业签定合作协议，共同评估Merrion公司开发的GIPET平台技术用于提高3个目标化合物口服生物利用度的效能。基于涵盖40多个化合物的数据库和21项临床试验结果比较，     

口服药物吸收促进剂应用与开发研究进展

目的 为口服药物吸收促进剂的合理使用及开发提供参考。方法 分析影响口服药物吸收的具体因素,结合国内外研究成果介绍吸收促进剂的常用种类及具体应用,阐述吸收促进剂增加肠道通透性、提高口服药物生物利用度的机制。结果与结论 口服药物生物利用度的影响因素包括消化道物理、化学屏障及药物处方组成等。口服药物吸收促进剂包括表面活性剂、螯合剂、壳聚糖及其衍生物、多肽类、聚酰胺-胺型树枝状大分子、生物黏附材料。表面活性剂为常用吸收促进剂,其一方面可提高药物的表观溶解度,进而提高亲脂性药物口服递送效率,另一方面可减少多种酶对药物的代谢作用,破坏消化道紧密连接、改善细胞膜流动性、促进肠淋巴转运吸收、增强药物与上皮细胞的亲和性,进而增加药物在消化道的渗透效率,从而提高口服生物利用度。目前能真正用于临床含吸收促进剂的药物仍较少,且安全性有待提高。     

肠道细胞色素P450和P-糖蛋白对口服药物生物利用度的影响

目的综述肠道细胞色素P450和P-糖蛋白(P-gp)对口服药物生物利用度的影响,包括CYP450、Pgp的作用及CYP与Pgp的联合作用。方法收集、阅读并分析近十年来关于肠道细胞CYP450和Pgp影响口服药物生物利用度的文献。结果 CYP450和Pgp在胃肠道均具有高表达,且两者的底物具有显著的重叠性,所以肠道细胞CYP450对已吸收药物的生物转化作用和肠道细胞中Pgp对已吸收药物的主动外排作用是影响口服药物生物利用度的重要因素。结论肠道细胞CYP450和Pgp对药物的口服生物利用度具有重要影响。     

肠壁CYP3A和P-糖蛋白与口服药物生物利用度

口服给药时 ,药物在到达腔静脉之前必先沿着胃肠道向下移动并通过肠壁和肝脏 ,加上大多数药物以原形发挥的药理活性 ,因此 ,口服生物利用度 (F)通常由药物吸收分数 (Fa)、吸收的药物不经代谢进入肝门脉血流的分数 (Fg)、肝首过利用度(进入肝脏的药物逃过首过消除的分数 ,Fh)三者所产生 ,即F=Fa×Fg×Fh。随着药物剂型的不断改进以及共用药物影响因素的尽量避免 ,近来认为药物在肠道的代谢以及被吸收药物在肠道的主动外排成了口服药物生物利用度的主要决定因素[1]。1细胞色素P450(CYP)3A位于许多组织滑面内质网上的CYPs是一组含亚铁血…     

生物利用度

生物利用度是反映所给药物进入病人体循环的药量比例。它描述口服药物由胃肠道吸收，及经过肝脏而到达体循环血液中的药量占口服剂量的百分比。药物的生物利用度，应考虑进入体循环的药量及速率两个方面。口服药物经胃肠道吸收而进入体循环的药量，通常以血药浓度一时间曲线的曲线下面积(AUC)计算。取决于药物的吸收及首过效应。生物利用度的速率，反映了口服后血药浓度峰值的出现时间及幅度。     

鼻腔给药的生物利用度研究进展

目前，鼻腔给药生物利用度的研究主要集中在吸收促进剂、药物性质、剂型和载体等因素的影响。虽然药物通过鼻腔吸收受诸多因素的影响，但由于鼻腔特殊的解剖生理结构，药物吸收迅速；且与其他给药途径相比，尤其对于多肽和蛋白类药物而言，鼻腔给药这种非侵入性给药方法更简单、安全并且节省费用，因此，有望成为未来全身给药的重要途径之一。本文综述了近年来药物经鼻腔给药的生物利用度的研究进展。     

药物外排泵和转运蛋白对口服药物吸收影响的研究进展

人体肠道的药物外排泵和转运蛋白对口服药物的吸收有较大影响,常见的药物外排泵有P-糖蛋白和多药耐药相关蛋白,会降低相关底物吸收;其它的一些转运蛋白如有机离子转运蛋白家族、H+/单羧酸共转运蛋白和肽转运蛋白可促进相关底物的吸收.作者对药物外排泵和转运蛋白近年来的相关研究进行了综述,并指出了药物外排泵和转运蛋白今后可能的研究方向.     

Novel revaprazan-loaded gelatin microsphere with enhanced drug solubility and oral bioavailability

Abstract

To develop a novel revaprazan-loaded gelatine microsphere with enhanced solubility and oral bioavailability, numerous gelatine microspheres were prepared using a spray-drying technique. The impact of gelatine amount on drug solubility in the gelatine microspheres was investigated. The physicochemical properties of the selected gelatine microsphere, such as shape, particle size and crystallinity, were evaluated. Moreover, its dissolution and pharmacokinetics in rats were assessed in comparison with revaprazan powder. Amongst the gelatine microspheres tested, the gelatine microsphere consisting of revaprazan and gelatine (1:2, w/w), which gave about 150-fold increased solubility, had the most enhanced drug solubility. It provided a spherical shape, amorphous drug and reduced particle size. Furthermore, it gave a higher dissolution rate and plasma concentration than did revaprazan powder. Particularly, it gave about 2.3-fold improved oral bioavailability in comparison with revaprazan powder. Therefore, this novel gelatine microsphere system is recommended as an oral pharmaceutical product of poorly water-soluble revaprazan.     

Solid lipid nanoparticles: an oral bioavailability enhancer vehicle

Introduction: The therapeutic efficacy of perorally administered drugs is often obscured by their poor oral bioavailability (BA) and low metabolic stability in the gastrointestinal tract (GIT). Solid lipid nanoparticles (SLNs) have emerged as potential BA enhancer vehicles for various Class II, III and IV drug molecules.

Area covered: This review examines the recent advancements in SLN technology, with regards to oral drug delivery. The discussion critically examines the effect of various key constituents on SLN absorption and their applications in oral drug delivery. The relationship between the complexity of absorption (and various factors involved during absorption, including particle size), stability and the self-emulsifying ability of the lipids used has been explored.

Expert opinion: The protective effect of SLNs, coupled with their sustained/controlled release properties, prevents drugs/macromolecules from premature degradation and improves their stability in the GIT. An extensive literature survey reveals that direct peroral administration of SLNs improves the BA of drugs by 2- to 25-fold. Overall, the ease of large-scale production, avoidance of organic solvents and improvement of oral BA make SLNs a potential BA enhancer vehicle for various Class II, III and IV drugs.     

Curcumin-loaded solid lipid nanoparticles with Brij78 and TPGS improved in vivo oral bioavailability and in situ intestinal absorption of curcumin

Abstract

Purpose: The present study was to formulate curcumin solid lipid nanoparticles (Cur-SLNs) with P-gp modulator excipients, TPGS and Brij78, to enhance the solubility and bioavailability of curcumin.

Methods: The formulation was optimized by Plackett–Burman screening design and Box–Behnken experiment design. Then physiochemical properties, entrapment efficiency and in vitro release of Cur-SLNs were characterized. In vivo pharmacokinetics study and in situ single-pass intestinal perfusion were performed to investigate the effects of Cur-SLNs on the bioavailability and intestinal absorption of curcumin.

Results: The optimized formulations showed an average size of 135.3?±?1.5?nm with a zeta potential value of ?24.7?±?2.1?mV and 91.09%?±?1.23% drug entrapment efficiency, meanwhile displayed a sustained release profile. In vivo pharmacokinetic study showed AUC_0→t for Cur-SLNs was 12.27-folds greater than curcumin suspension and the relative bioavailability of Cur-SLNs was 942.53%. Meanwhile, T_max and t_1/2 of curcumin for Cur-SLNs were both delayed comparing to the suspensions (p?<?0.01). The in situ intestinal absorption study revealed that the effective permeability (P_eff) value of curcumin for SLNs was significantly improved (p?<?0.01) comparing to curcumin solution.

Conclusion: Cur-SLNs with TPGS and Brij78 could improve the oral bioavailability and intestinal absorption of curcumin effectively.     

Emerging role of nanocarriers to increase the solubility and bioavailability of curcumin

Introduction: Curcumin is a safe, affordable and natural bioactive molecule of turmeric (Curcuma longa). It has gained considerable attention in recent years for its multiple pharmacological activities. However, its optimum pharmaceutical potential has been limited by its lack of aqueous solubility and poor bioavailability. To mitigate the above limitations, recently various nanostructured water-soluble delivery systems were developed to increase the solubility and bioavailability of curcumin.

Areas covered: Major reasons contributing to the low bioavailability of curcumin appear to be owing to its poor solubility, low absorption, rapid metabolism and rapid systemic elimination. The present review summarizes the strategies using curcumin in various nanocarrier delivery systems to overcome poor solubility and inconsistent bioavailability of curcumin and describes the current status and challenges for the future.

Expert opinion: The development of various drug delivery systems to deliver curcumin will certainly provide a step up towards augmenting the therapeutic activity of curcumin thereby increasing the solubility and bioavailability of curcumin. However, the future of such delivery technology will be highly dependent on the development of safe, non-toxic and non-immunogenic nanocarriers.     

Novel piroxicam-loaded nanospheres generated by the electrospraying technique: physicochemical characterisation and oral bioavailability evaluation

To determine if a novel electrospraying technique could be applied to an oral drug delivery system for improving the solubility and oral bioavailability of poorly water-soluble piroxicam; the nanospheres were generated with drug and polyvinylpyrrolidone (PVP) using electrospraying technique; and their physicochemical properties, solubility, release and pharmacokinetics were evaluated in comparison with piroxicam powder. All nanospheres had significantly increased drug solubility and dissolution rates in comparison with the drug powder. In particular, the nanosphere composed of piroxicam and PVP at a weight ratio of 2:8 gave about 600-fold higher solubility, 15-fold higher release rate and 3-fold higher AUC in comparison to piroxicam powder, leading to significantly enhanced oral bioavailability in rats, due to the mingled effect of nanonisation along with transformation to the amorphous state. Thus, this electrospraying technique can be utilised to produce a novel oral nanosphere delivery system with enhanced solubility and oral bioavailability for poorly water-soluble piroxicam.     

阿苯达唑-盐酸盐的制备、表征及口服生物利用度的评价

目的 制备阿苯达唑（ABZ）-盐酸（HCl）盐（ABZ-HCl）,并对盐的固态性质、体外溶出行为、稳定性和生物利用度进行评价。方法 溶剂蒸发法制备结晶的ABZ-HCl,使用核磁共振氢谱（¹H-NMR）对制备的ABZ-HCl进行验证,通过粉末X射线衍射（PXRD）、动态水吸附（DVS）、热重分析（TGA）和差示扫描量热法（DSC）进行固态性质的表征;对药物盐进行表观溶解度和固有溶出速率（IDR）的测定以观察其在不同pH条件下溶解度和溶出速率;进行了ABZ-HCl在强光照射（4 500±500 lx）、高湿（92.5%±5% RH）和高温条件（50±2）℃,以及加速试验条件（40℃、75%±5% RH）的稳定性研究;评价ABZ、ABZ-HCl （25 mg·kg^-1）在大鼠体内的药动学行为差异。结果 通过¹H-NMR证实了ABZ-HCl的形成;ABZ和ABZ-HCl的PXRD图谱出现显著差异;DVS实验结果表明,ABZ原药的吸水性差,在90%相对湿度（RH）时吸水量仅为3.86%,且吸附与解吸附曲线基本重合,而ABZ-HCl在开始的0~20% RH范围内迅速吸收水分,随后质量缓慢增加,在RH达到90%时吸水量为37.65%,在解吸过程中,ABZ-HCl的吸附曲线和解吸曲线不一致,存在滞后现象;TGA和DSC实验结果表明,2种物质均无吸附水,ABZ-HCl较ABZ熔点降低;体外溶出实验结果显示ABZ-HCl的表观溶解度和IDR分别为ABZ的11.8、10.3倍;ABZ-HCl表现出良好的物理稳定性。体内药动学结果显示,与ig ABZ原料相比,ABZ-HCl的AUC_{0~24 h}和C_max均显著提高,分别提高了8.8和6.9倍。结论 所制备的ABZ-HCl可改善ABZ的溶解性能和口服生物利用度,且具有良好的物理稳定性。     

肠道“药物代谢酶-外排转运体偶联”对黄酮类化合物生物利用度影响的研究进展

黄酮类化合物为广泛存在于食物和药物中的一类多酚化合物，具有多种药理作用，但其生物利用度低限制了其临床应用，这与其肠道吸收和代谢密切相关。黄酮类化合物主要在肠道吸收，并经Ⅱ相药物代谢酶：葡萄糖醛酸转移酶（UGTs），硫酸转移酶（SULTs）和谷胱甘肽-S-转移酶（GSTs）广泛代谢为Ⅱ相代谢产物，其极性增加，难以通过被动扩散穿透肠上皮细胞膜。肠道外排转运体P-糖蛋白（P-gp）、乳腺癌耐药蛋白（BCRP）、多药耐药相关蛋白（MRPs）作为一个"旋转门"，可调控肠上皮细胞内Ⅱ相代谢物外排至肠腔或进入体循环。本文对黄酮类化合物在肠道处置以及肠道药物代谢酶-外排转运体偶联进行了探究，这种偶联作用可显著影响黄酮类化合物生物利用度，进而影响其临床疗效与毒副作用。阐明肠道代谢酶-外排转运体偶联作用及其机制，将为提高黄酮类化合物体内生物利用度和增加其临床疗效奠定基础。     

Triglyceride-mimetic prodrugs of scutellarin enhance oral bioavailability by promoting intestinal lymphatic transport and avoiding first-pass metabolism

The intestinal capillary pathway is the most common way to absorb oral drugs, but for drugs with poor solubility and permeability and high first-pass metabolism, this pathway is very inefficient. Although intestinal lymphatic transport of lipophilic drugs or prodrugs is a promising strategy to improve the oral delivery efficiency of these drugs. The prodrug strategy for modifying compounds with Log P > 5 to promote intestinal lymphatic transport is a common approach. However, transport of poor liposoluble compounds (Log P < 0) through intestinal lymph has not been reported. Herein, triglyceride-mimetic prodrugs of scutellarin were designed and synthesized to promote intestinal lymphatic transport and increase oral bioavailability. Lymphatic transport and pharmacokinetic experiments showed that two prodrugs did promote intestinal lymphatic transport of scutellarin and the relative oral bioavailability was 2.24- and 2.45-fold of scutellarin, respectively. In summary, triglyceride-mimetic prodrugs strategy was used for the first time to study intestinal lymphatic transport of scutellarin with Log P < 0, which could further broaden the application range of drugs to improve oral bioavailability with the assistance of intestinal lymphatic transport.