共查询到18条相似文献,搜索用时 176 毫秒
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药物在肠道内的吸收程度和吸收特征是影响口服药物生物利用度的重要因素。肠道吸收研究可以预测影响药物在肠道吸收的机制与因素,研究方法主要包括体内法(in vivo)、在体法(in situ)、体外法(in vitro)等。就目前药物小肠吸收的研究方法及其特点进行综述。 相似文献
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药物肠道吸收研究方法 总被引:2,自引:0,他引:2
药物在肠道内的吸收程度和吸收特征是影响口服药物生物利用度的重要因素。肠道吸收研究可以预测影响药物在肠道吸收的机制与因素,研究方法主要包括体内法(invivo)、在体法(insitu)、体外法(invitro)等。就目前药物小肠吸收的研究方法及其特点进行综述。 相似文献
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甲氨蝶呤是一种抗叶酸类抗肿瘤药物,临床常用于治疗某些肿瘤性疾病、风湿性关节炎和银屑病,治疗作用显著,但治疗窗较窄。多种转运体参与甲氨蝶呤在体内的处置过程,当甲氨蝶呤与其他药物合用时,易发生基于转运体的药物相互作用,从而导致药物的不良反应或药物疗效的改变。本文通过查阅及分析文献,总结归纳了转运体介导的甲氨蝶呤与其他药物间的相互作用,为甲氨蝶呤的临床合理用药提供参考。 相似文献
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药物转运蛋白功能及应用 总被引:3,自引:0,他引:3
细胞膜转运蛋白是一些药物的吸收、分布和消除的决定因素,具有重要的药剂学意义。作为异生物质排出细胞的通道,ABC转运蛋白对大多数现在使用的药物的体内行为产生重要影响,包括治疗肿瘤、艾滋病和微生物感染用药。小肽转运蛋白具有广谱的底物特异性.能够转运大量的口服的结构类似于小肽的药物。由于新的小肽和多肽模拟物类药物的迅速增加,小肽转运蛋白因可能成为药物转运系统而倍受关注。在分子水平加深对药物转运蛋白的理解势必促进药物设计与生物药剂学的发展。 相似文献
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目的对肝脏转运蛋白在药物肝胆转运中的作用作一综述,为药物肝靶向提供依据。方法根据文献,从药物不良反应、药物的矢量转运、药物肝靶向性、药物之间相互作用4个方面阐述肝脏转运蛋白对药物肝胆排泄产生的影响。结果肝脏转运蛋白引起的药物矢量转运影响药物的肝脏摄取,药物肝靶向性影响药物的疗效,药物之间相互作用影响临床用药安全和不良反应。结论肝脏转运蛋白在药物肝胆转运中起到了重要的作用,它与药物在体内各组织分布、临床疗效均有密切的联系。 相似文献
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口服药物肠道吸收的研究方法主要包括体外法、体内法和在体法,对这3种研究方法进行简要介绍。鉴于在体肠灌流法操作简便、技术成熟、可控性强,同时又保证了神经内分泌调节与淋巴液血液供应的完整性等特点,更能反映药物吸收的真实情况,因此重点介绍了在体肠灌流法,并对在体肠灌流法中使用的循环灌流法和单向灌流法常用的几种灌流液体积校正方法等进行综述,为研究口服药物肠道吸收试验设计提供借鉴和参考。为保证试验的可操作性和实验结果的准确性,认为应根据所研究药品的性质、实验要求、试验条件等多方面因素综合考虑,选择适宜的试验方法,进而为药物剂型的开发和临床合理用药提供依据。 相似文献
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Members of the solute carrier (SLC) 36 family are involved in transmembrane movement of amino acids and derivatives. SLC36 consists of four members. SLC36A1 and SLC36A2 both function as H(+) -coupled amino acid symporters. SLC36A1 is expressed at the luminal surface of the small intestine but is also commonly found in lysosomes in many cell types (including neurones), suggesting that it is a multipurpose carrier with distinct roles in different cells including absorption in the small intestine and as an efflux pathway following intralysosomal protein breakdown. SLC36A1 has a relatively low affinity (K(m) 1-10 mM) for its substrates, which include zwitterionic amino and imino acids, heterocyclic amino acids and amino acid-based drugs and derivatives used experimentally and/or clinically to treat epilepsy, schizophrenia, bacterial infections, hyperglycaemia and cancer. SLC36A2 is expressed at the apical surface of the human renal proximal tubule where it functions in the reabsorption of glycine, proline and hydroxyproline. SLC36A2 also transports amino acid derivatives but has a narrower substrate selectivity and higher affinity (K(m) 0.1-0.7 mM) than SLC36A1. Mutations in SLC36A2 lead to hyperglycinuria and iminoglycinuria. SLC36A3 is expressed only in testes and is an orphan transporter with no known function. SLC36A4 is widely distributed at the mRNA level and is a high-affinity (K(m) 2-3 μM) transporter for proline and tryptophan. We have much to learn about this family of transporters, but from current knowledge, it seems likely that their function will influence the pharmacokinetic profiles of amino acid-based drugs by mediating transport in both the small intestine and kidney. 相似文献
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Caco-2细胞模型在口服药物吸收研究中的应用 总被引:1,自引:0,他引:1
目的对Caco 2细胞模型在口服药物肠吸收研究中的应用作一综述。方法在引用了自1974~2004年的32篇文献的基础上,通过介绍并比较体外Caco 2模型和体内药物吸收转运的不同途径,讨论Caco 2单层细胞模型在预测不同类药物体内吸收中的作用。结果Caco 2细胞模型可以预测不同转运途径的药物体内吸收,尤其适用于被动转运药物,这一细胞模型在药物吸收机制、处方组成透膜性和黏膜毒性、药物吸收过程中的相互作用、药物的化学结构和体内转运关系、药物吸收限速因素、药物代谢稳定性及pH对药物吸收的影响等研究中均有较广泛的应用。结论Caco2细胞模型用于预测各种途径的药物吸收,在细胞水平上提供了大量与吸收相关的信息,是口服药物高通量筛选的良好工具。 相似文献
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M. Nagao H. Saitoh W. D. Zhang K. Iseki Y. Yamada T. Takatori K. Miyazaki 《Archives of toxicology》1993,67(4):262-267
The mechanism of absorption of paraquat, which is a type of quaternary ammonium compound (QAC), was studied using rat intestinal loops and brushborder membrane vesicles. Approximately 47% and 37% of radioactively labeled paraquat injected into jejunal and ileal loops disappeared, respectively, after 60 min. Since only a small amount of radioactivity was detected in the mucosal fraction, most of the paraquat that disappeared from the intestinal lumen was considered to have been carried away by the bloodstream, indicating that paraquat absorption was greater than expected. In spite of its low lipid solubility, the uptake of paraquat by brush-border membrane vesicles reflected smooth penetration into the intravesicular space rather than binding to the membrane. According to the increase in extravesicular paraquat concentration, paraquat uptake in the early stage was saturable. Moreover, early paraquat uptake was significantly inhibited by structurally-related QACs such as tetramethylammonium and choline, but not by an endogenous dicationic amine (putrescine). On the other hand, inside-negative membrane potential had no significant effect on the time course of paraquat uptake. From these results, it is suggested that paraquat is absorbed through a specialized mechanism associated with the carrier-mediated transport system for choline on the brush-border membrane. 相似文献
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Okumura Shigeki Fukuda Yoshimi Takahashi Kanae Fujita Takuya Yamamoto Akira Muranishi Shozo 《Pharmaceutical research》1996,13(8):1247-1251
Purpose. The permeability of drugs across the Xenopus pulmonary membrane and the effects of various absorption enhancers on their absorption were examined using an in vitro Ussing chamber technique.
Methods. Phenol red and fluorescein isothiocyanate-labeled dextrans (FDs) with different molecular weights were chosen as water-soluble model drugs. Absorption enhancers used in this study were N-lauryl--D-maltopyranoside (LM), linoleic acid-HCO60 mixed micelle (MM), sodium glycocholate (Na-GC), sodium caprate (Na-Cap), sodium salicylate (Na-Sal) and disodium EDTA (EDTA).
Results. The permeability of drugs gradually decreased with increasing their molecular weights, and the absorption of phenol red significantly increased by these absorption enhancers. Among these additives, LM, MM and Na-Cap appeared to be more effective for enhancing the permeability of drugs than the others. Furthermore, we plotted the logarithm of apparent permeability coefficient (Papp) of these drugs against the logarithm of their molecular weights. There exists a good correlation between these parameters. We measured transmembrane resistance(Rm) of Xenopus pulmonary membrane during the transport experiment to examine the membrane integrity. The average Rm value was about 700 ·crn2, and this value was maintained for 3 hr.
Conclusions. This method is useful for estimating the transport characteristics of drugs across the pulmonary membrane. 相似文献
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Contribution of equilibrative nucleoside transporter(s) to intestinal basolateral and apical transports of anticancer trifluridine 下载免费PDF全文
Koichi Takahashi Kunihiro Yoshisue Masato Chiba Takeo Nakanishi Ikumi Tamai 《Biopharmaceutics & drug disposition》2018,39(1):38-46
Trifluridine (FTD) exhibits anticancer activities after its oral administration despite its hydrophilic nature. It was previously reported that concentrative nucleoside transporter (CNT) 1 mediates the apical uptake of FTD in human small intestinal epithelial cells (HIECs). In the present study, FTD was also identified as a substrate for equilibrative nucleoside transporter (ENT) 1 and ENT2 in transporter gene‐transfected cells. An immunocytochemical analysis revealed that ENT1 was expressed at the basolateral and apical membranes of HIECs. Cellular accumulation increased in the presence of S‐(4‐nitrobenzyl)‐6‐thioinosine (NBMPR), an ENT selective inhibitor. Cytotoxicity in HIEC monolayers at low FTD concentrations was increased by NBMPR, and this may have been due to inhibition of the ENT‐mediated basolateral transport of FTD by NBMPR. These results suggest that ENTs reduce the intestinal cytotoxicity of FTD by facilitating its basolateral efflux. On the other hand, the intracellular accumulation and cytotoxicity of FTD in HIECs were decreased at higher concentrations of FTD by NBMPR, and this may have been due to the NBMPR inhibition of the apical uptake of FTD, which has been suggested to be mediated by CNTs and ENTs. In conclusion, ENTs were responsible for intestinal transepithelial permeation by mediating the basolateral efflux of FTD after its uptake by CNT1 from the apical side, resulting in decreases in its intracellular accumulation and intestinal toxicity in humans. Equilibrative nucleoside transporters may also partially contribute to the low‐affinity uptake of FTD across the apical membrane along with high‐affinity CNT1. 相似文献