In vitro and In vivo Interaction of Ketorolac Tromethamine and Cefixime Trihydrate

Mokaddas Flora, Rafat Tahsin, J. A. Chowdhury, Shaila Kabir, Md. Shah Amran, A. A. Chowdhury
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Abstract

Drug-drug interaction, a major impediment towards safe and effective pharmacotherapy, often leads to adverse outcome or therapeutic failure if not properly identified. The present study employed a number of in vitro and in vivo methods to conduct a thorough investigation of the interaction potential between ketorolac tromethamine (nonsteroidal anti-inflammatory drug) and cefixime trihydrate (beta-lactam antibiotic). UV-Visible spectrophotometry, FTIR and DSC were carried out to analyze the interaction of ketorolac and cefixime in vitro. UV-visible spectrophotometric study at different pH showed hyperchromic shift and blue shift (hypsochromic shift) in the mixture of the studied drugs compared to ketorolac alone. In contrast, only hyperchromic shift was found in the mixture when compared to cefixime alone. In DSC study, the melting endotherm of ketorolac tromethamine shifted from 169.62°C to 149.99°C in the 1:1 mixture. Again, the FTIR spectrum showed that in 1:1 mixture, the lactam (C=O) band of cefixime trihydrate shifted from 1771.68 cm-1 to 1718.63 cm-1, the amide carbonyl band (-CONH) moved from 1669.45 cm-1 to 1616.4 cm-1 and the -OH band moved from 3296.46 cm-1 to 3397.72 cm-1 which might be indicative of interaction between these two drugs. The in vivo study in rat model was designed to determine whether cefixime has any significant impact on the analgesic activity of ketorolac. In vitro  antimicrobial effect was also performed to evaluate the effect of ketorolac on cefixime. The findings from these study suggested that neither ketorolac nor cefixime imparted any deleterious impact on the biological property of each other which might indicate that co-administration of ketorolac and cefixime are therapeutically effective and safe. Dhaka Univ. J. Pharm. Sci. 22(2): 137-146, 2023 (December)
酮咯酸氨丁三醇和三水头孢克肟的体外和体内相互作用
药物相互作用是实现安全有效药物治疗的主要障碍,如果不能正确识别,往往会导致不良后果或治疗失败。本研究采用了多种体外和体内方法,对酮咯酸氨丁三醇(非甾体抗炎药)和三水合头孢克肟(β-内酰胺类抗生素)之间的相互作用潜力进行了深入研究。采用紫外-可见分光光度法、傅立叶变换红外光谱法和 DSC 分析酮咯酸和头孢克肟在体外的相互作用。在不同 pH 值下进行的紫外-可见分光光度法研究显示,与单独的酮咯酸相比,所研究药物的混合物出现了高色移和蓝移(低色移)。相反,与单独的头孢克肟相比,混合物中只出现了高色移。在 DSC 研究中,在 1:1 的混合物中,酮咯酸氨丁三醇的熔化温度从 169.62°C 下降到 149.99°C。同样,傅立叶变换红外光谱显示,在 1:1 混合物中,头孢克肟三水合物的内酰胺(C=O)带从 1771.68 cm-1 移至 1718.63 cm-1,酰胺羰基带(-CONH)从 1669.45 cm-1 移至 1616.4 cm-1,-OH 带从 3296.46 cm-1 移至 3397.72 cm-1,这可能表明这两种药物之间存在相互作用。大鼠模型体内研究旨在确定头孢克肟对酮咯酸的镇痛活性是否有明显影响。此外,还进行了体外抗菌效果研究,以评估酮咯酸对头孢克肟的影响。这些研究结果表明,酮咯酸和头孢克肟都不会对彼此的生物特性产生任何有害影响,这可能表明酮咯酸和头孢克肟联合用药既有效又安全。达卡大学药学学报》(Dhaka Univ.22(2):137-146,2023 年(12 月)
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