昂丹西琼口服溶液与透皮侵润凝胶在大鼠体内药动学参数的比较研究

Omar S. Salih, E. J. Al-Akkam
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引用次数: 1

摘要

本研究旨在比较昂丹司琼经皮(作为侵入体凝胶)和口服(作为溶液)两种途径的药代动力学参数。昂丹司琼是一种5 -羟色胺受体拮抗剂,用于化疗和放疗引起的恶心和呕吐。选用体重200±20 g的Wistar白化大鼠分为两组,每组6只。第一组口服剂量为0.28 mg,相当于140µl的昂丹司琼。制备并优化负载昂丹司琼的入侵体凝胶,并以0.1652 mg昂丹司琼的剂量涂抹在大鼠皮肤上,第二组相当于41 mg重量的入侵体凝胶。另外,采用高效液相色谱法测定大鼠血浆中的昂丹司琼,经验证后采用改进的高效液相色谱法。比较两种途径的主要药代动力学参数。结果表明,cmax、tmax、AUC 0 ~ 24、AUC 0 ~∞分别为58±3.4 ng/ml、2±0.2 h、246.25±47.6 ng.h。口服液分别为36±2.9 ng/ml, 5±0.5 h, 390.5±5.2 ng.h, 259.4±57.7。442.8±66.1 ng.h./ml。,分别为透皮侵润凝胶。结果表明,口服和透皮两种途径达到最大效果所需的时间和浓度(cmax和tmax)差异有统计学意义(p <0.05)。单次给药24 h后,经皮给药途径的相对生物利用度是口服给药途径的2.9倍。综上所述,制备的侵体凝胶增强了昂丹西酮的生物利用度,可以认为经皮给药是昂丹西酮的重要给药系统。
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Pharmacokinetic parameters of ondansetron in rats after oral solution and transdermal invasomes gel: A comparison study
This study aimed to attain a comparison in pharmacokinetic parameters of ondansetron after transdermal (as invasomes gel) and oral (as solution) routes. Ondansetron is a 5 ‐ hydroxytryptamine receptor antagonist used for chemotherapy and radiotherapy ‐ induced nausea and emesis. The study was performed using Wistar albino rats weighing 200 ±20 g divided into two groups (6 of each). A dose of 0.28 mg of ondansetron, equivalent to 140 µl, was administered as an oral solution for the first group. Ondansetron-loaded invasomes gel was prepared, optimized, and applied on rat skin at a dose of 0.1652 mg of ondansetron, equivalent to 41 mg weight of invasomes gel for the second group. In addition, ondansetron was determined in rat plasma using HPLC apparatus and applying a modified HPLC method after validation. A comparison of primary pharmacokinetic parameters for both routes was performed. Results showed that C max , T max , AUC 0-24, and AUC 0-∞ were 58±3.4 ng/ml, 2±0.2 h., 246.25±47.6 ng.h./ml, and 259.4±57.7, respectively, for oral solution and 36±2.9 ng/ml, 5±0.5 h., 390.5±5.2 ng.h./ml and 442.8±66.1 ng.h./ml., respectively for transdermal invasomes gel. Results showed that the time and concentration needed to achieve the maximum effect (C max and T max ) were significantly different between oral and transdermal routes ( p <0.05). The relative bioavailability for the transdermal route was 2.9 times that of the oral route after a single dose administered for 24 h. In conclusion, the prepared invasomes gel enhanced the bioavailability of ondansetron, and transdermal delivery could be considered a vital delivery system for ondansetron.
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期刊介绍: Journal of Advanced Pharmacy Education & Research [JAPER] aims to explore the knowledge of pharmacy professionals and cater the need of research and development activities of both academia and Industries. Further, also aimed to bridge the gap between theoretical aspects of drug delivery concepts and practical clinical studies to make sure of the novel drug delivery system usefulness in health care system. The Journal having scope for researchers engaged in drug delivery field to utilize the scientific contents in a rightful way. Journal of Advanced Pharmacy Education & Research [JAPER], a broad-based journal was founded on two key tenets: To publish the most exciting researches with respect to the subjects of Pharmaceutical science. Secondly, to provide a rapid turn-around time possible for reviewing and publishing, and to disseminate the articles freely for research, teaching and reference purposes. Our objective is to inform authors of the decision on their manuscript as early as possible. Following acceptance, a paper will normally be published in the next available issue. Journal of Advanced Pharmacy Education & Research [JAPER], is using online manuscript submission, review and tracking system for quality and quick review processing. Review processing is performed by the editorial board members of JAPER, outside experts; at least two independent reviewers approval followed by editor approval is required for acceptance of any citable manuscript.
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