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口服给予新配制的藻酸盐/阿拉伯胶包载酮康唑微珠在兔血浆中的药代动力学评价

Pharmacokinetics evaluation of newly formulated beads alginate/gum acacia loaded ketoconazole in rabbit plasma by oral administration.

作者信息

Annisa Viviane, Sulaiman Teuku Nanda Saifullah, Nugroho Akhmad Kharis, Nugroho Agung Endro

机构信息

Program Doctoral Faculty of Pharmacy, Universitas Gadjah Mada, Indonesia.

Departement of Pharmaceutics, Faculty of Pharmacy, Universitas Gadjah Mada, Indonesia.

出版信息

ADMET DMPK. 2023 Nov 30;12(2):335-341. doi: 10.5599/admet.2042. eCollection 2024.


DOI:10.5599/admet.2042
PMID:38720931
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11075158/
Abstract

BACKGROUND AND PURPORSE: The combination of alginate and gum acacia in previous studies showed good results in inhibiting ketoconazole precipitation due to the supersaturation phenomenon. Ketoconazole-loaded alginate and gum acacia can produce hydrogel beads through cross-linking with Ca using ionotropic gelation techniques. However, the pharmacokinetic study of the ketoconazole beads loaded to alginate and gum acacia needs further investigation. This study aimed to evaluate pharmacokinetic parameters using rabbits via oral administration. EXPERIMENTAL APPROACH: The drug was administered orally to 2 groups of rabbits: pure ketoconazole (KTZ) and formulation of ketoconazole (AG75) groups. Blood samples were obtained from the ear marginal vein at various time points: 0 (before administration), 15, 30, 45, 60, 90, 120, 150, 180, 240, 300, 360, and 420 minutes after oral dosage. The pharmacokinetic study employed a non-compartment analysis to calculate the area under the curve (AUC), the volume of distribution ( ), clearance (), maximum concentration (), and time to reach maximum concentration (). The data obtained from the parameter result was analyzed using the independent-sample T-test. KEY RESULT: The results of the KTZ group include AUC of 15.83±0.62 h μg mL, of 8.95±1.17 mL, of 3.45±0.3 mL h, of 4.7±0.69 μg mL, and of 1.67±0.17 h. The results of the AG75 group include AUC of 27.8±1.01 h μg mL, of 11.5±2.4 mL, of 2.15±0.11 mL h, of 4.49±0.52 μg mL, and of 2.5±0.5 h. CONCLUSION: The formulation incorporating ketoconazole beads resulted in a higher AUC than the pure ketoconazole. This finding suggests that the created formulation has enhanced the bioavailability of ketoconazole.

摘要

背景与目的:在先前的研究中,海藻酸盐与阿拉伯胶的组合在抑制因过饱和现象导致的酮康唑沉淀方面显示出良好效果。负载酮康唑的海藻酸盐和阿拉伯胶可通过离子凝胶化技术与钙交联产生水凝胶珠。然而,负载于海藻酸盐和阿拉伯胶的酮康唑珠的药代动力学研究需要进一步探究。本研究旨在通过口服给药对家兔进行药代动力学参数评估。 实验方法:将药物口服给予两组家兔:纯酮康唑(KTZ)组和酮康唑制剂(AG75)组。在各个时间点从耳缘静脉采集血样:口服给药后0(给药前)、15、30、45、60、90、120、150、180、240、300、360和420分钟。药代动力学研究采用非房室分析来计算曲线下面积(AUC)、分布容积( )、清除率()、最大浓度()以及达到最大浓度的时间()。从参数结果获得的数据使用独立样本T检验进行分析。 关键结果:KTZ组的结果包括AUC为15.83±0.62 h·μg/mL, 为8.95±1.17 mL, 为3.45±0.3 mL/h, 为4.7±0.69 μg/mL, 为1.67±0.17 h。AG75组的结果包括AUC为27.8±1.01 h·μg/mL, 为11.5±2.4 mL, 为2.15±0.11 mL/h, 为4.49±0.52 μg/mL, 为2.5±0.5 h。 结论:包含酮康唑珠的制剂导致AUC高于纯酮康唑。这一发现表明所制备的制剂提高了酮康唑的生物利用度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c395/11075158/d68a22d6b530/ADMET-12-2042-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c395/11075158/ed596064e636/ADMET-12-2042-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c395/11075158/d68a22d6b530/ADMET-12-2042-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c395/11075158/ed596064e636/ADMET-12-2042-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c395/11075158/d68a22d6b530/ADMET-12-2042-g002.jpg

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本文引用的文献

[1]
Formulation, Characterization and Biological Activity Screening of Sodium Alginate-Gum Arabic Nanoparticles Loaded with Curcumin.

Molecules. 2020-5-10

[2]
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J Pharm Sci. 2018-11-10

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