同时服用抗逆转录病毒药物和抗疟疾药物之间的理化相互作用

IF 2.7 4区医学 Q2 PHARMACOLOGY & PHARMACY Journal of Pharmaceutical Innovation Pub Date : 2024-10-21 DOI:10.1007/s12247-024-09872-4

Vullendula Sai Krishna Anand, Dani Lakshman Yarlagadda, Athira R. Nair, Krishnamurthy Bhat, Swapnil J. Dengale

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引用次数: 0

摘要

方法分别研究了抗疟固定剂量复方制剂，即蒿甲醚（A）和乐凡啶（L）与奈韦拉平（N）或依非韦伦（E）之间的理化相互作用。对物理混合物（ALE 和 ALN）进行了溶解度、pH 值偏移溶解度（在磷酸盐和生物相关介质中）、固态表征和体内外渗透性研究。结果对于蒿甲醚-乐凡妥+依非韦伦（ALE）系统，pH 值偏移溶解度研究表明，在乐凡妥和依非韦伦存在的情况下，混合物中的蒿甲醚浓度降至纯药溶解度的一半。此外，固态表征也证实了蒿甲醚在 Lumefantrine 和 Efavirenz 的存在下原位转化为无定形形式。同样，在体外恒温肠囊渗透性研究中，由于物理化学相互作用，蒿甲醚在有Lumefantrine和Efavirenz存在时的渗透性比单独使用蒿甲醚时降低了一半。对于蒿甲醚-鲁米班亭+奈韦拉平（ALN）系统，蒿甲醚的溶解度与单独使用时相比没有明显变化。然而，蒿甲醚的渗透性在乐凡妥和奈韦拉平的作用下降低到纯药渗透性的一半，这可能是由于奈韦拉平诱导了细胞色素 P450 3A4 和 P 糖蛋白酶。结论在抗逆转录病毒药物存在的情况下，混合物中蒿甲醚的溶解度和渗透性降低到纯药溶解度和渗透性的一半，这可能是由于物理化学相互作用导致生物利用度降低。这项研究结果表明，同时服用这些药物可能会因理化相互作用而导致治疗失败。

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Physicochemical Interactions Between Concomitantly Administered Anti-Retroviral and Anti-Malarial Drug

Purpose

To investigate the physicochemical interactions between concomitantly administered anti-malarial and antiretroviral drugs.

Methods

The physicochemical interactions between antimalarial fixed dose combination i.e., Artemether (A) and Lumefantrine (L) with Nevirapine (N) or Efavirenz (E) were investigated separately. The physical mixtures (ALE and ALN) were subjected to solubility, pH shift dissolution (in phosphate and biorelevant media), solid-state characterisation and ex-vivo permeability studies.

Results

For Artemether-Lumefantrine + Efavirenz (ALE) system, the pH shift dissolution study revealed that artemether concentration in mixture decreased to half of its pure drug dissolution in the presence of Lumefantrine and Efavirenz. Further, solid state characterisation confirms the in-situ conversion of artemether into amorphous form in the presence of Lumefantrine and Efavirenz. Similarly, in the ex-vivo everted gut sac permeability study, permeability of Artemether in the presence of Lumefantrine and Efavirenz decreased by half compared to the permeability of Artemether alone, due to physicochemical interactions. For Artemether-Lumefantrine + Nevirapine (ALN) system, there was no significant change in the dissolution of artemether from the combination and alone. However, the permeability of Artemether was decreased to half of its pure drug permeability in the presence of Lumefantrine and Nevirapine, which may be attributed to the inducation of Cytochrome P450 3A4 and P-glycoprotein enzyme by Nevirapine.

Conclusion

The dissolution and permeability of Artemether in the mixtures were reduced to half of its pure drug dissolution and permeability in the presence of antiretroviral drugs due to physicochemical interactions, which may lead to a decrease in bioavailability. This study’s results reveal concomitant administration of these drugs could lead to treatment failure due to physicochemical interactions.

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来源期刊

Journal of Pharmaceutical Innovation PHARMACOLOGY & PHARMACY-

CiteScore

3.70

自引率

3.80%

发文量

审稿时长

>12 weeks

期刊介绍： The Journal of Pharmaceutical Innovation (JPI), is an international, multidisciplinary peer-reviewed scientific journal dedicated to publishing high quality papers emphasizing innovative research and applied technologies within the pharmaceutical and biotechnology industries. JPI''s goal is to be the premier communication vehicle for the critical body of knowledge that is needed for scientific evolution and technical innovation, from R&D to market. Topics will fall under the following categories: Materials science, Product design, Process design, optimization, automation and control, Facilities; Information management, Regulatory policy and strategy, Supply chain developments , Education and professional development, Journal of Pharmaceutical Innovation publishes four issues a year.