在类风湿关节炎啮齿动物模型中,个体和盒状给药对强的松龙、双氯芬酸和甲氨蝶呤药代动力学的影响。

IF 1.2 Q4 PHARMACOLOGY & PHARMACY
Satish Kumar, Surendra Yadav Ravulapalli, Satinder Singh, Sumeet Gupta, Pratima Srivastava
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引用次数: 0

摘要

目的:为了了解关节炎疾病如何影响泼尼松龙、双氯芬酸和甲氨蝶呤在雄性Sprague- Dawley大鼠中单独或以盒状给药的药代动力学,本研究的主要目的是研究药物-药物相互作用(DDI)。对于中重度关节炎的治疗,医生通常会单独或联合使用这三种药物。方法:在雄性Sprague-Dawley大鼠禁食状态下,采用单药和盒式给药的方法评估药代动力学(PK)。实验组分别口服强的松龙(5.0 mg/kg)、双氯芬酸(10.0 mg/kg)和甲氨蝶呤(0.5 mg/kg),剂量体积为5ml /kg。经颈静脉采血,采用液相色谱-串联质谱法分析。采用Phoenix软件8.1版计算药代动力学参数。结果:与独立正常动物组相比,强的松龙明显降低了关节炎组和卡带组的AUC0-last。正常组盒式给药和关节炎组离散给药均不影响双氯芬酸的药代动力学(PK)。然而,在关节炎组中,双氯芬酸的AUC0-last值在卡式给药期间显著降低。关节炎组单独给予甲氨蝶呤导致AUC0-last显著下降,而健康组作为卡带给予时,AUC0-last显著增加。结论:与药理学DDI一起,本研究观察了疾病如何影响泼尼松龙、双氯芬酸和甲氨蝶呤在分立剂量和盒式剂量下的PK。在关节炎组中,强的松龙和甲氨蝶呤药代动力学的AUC0-t和Cmax在作为一个盒或单独睡眠时有显著差异。甲氨蝶呤与双氯芬酸联用时血清甲氨蝶呤浓度升高。此外,当与强的松龙联合使用时,甲氨蝶呤的代谢增加。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Impact of Individual and Cassette Administration on Pharmacokinetics of Prednisolone, Diclofenac, and Methotrexate in a Rodent Model of Rheumatoid Arthritis.

Objectives: To find out how arthritic diseases affect the pharmacokinetics of prednisolone, diclofenac, and methotrexate when given individually and as a cassette in male Sprague- Dawley rats, the study's main goal was to look into drug-drug interactions (DDI). For the treatment of moderate to severe arthritis, doctors commonly prescribe all three drugs alone or in combination.

Methodology: Pharmacokinetics (PK) was evaluated using individual and cassette dosing in male Sprague-Dawley rats in a fasting state. Respective experimental groups were administered orally with prednisolone (5.0 mg/kg), diclofenac (10.0 mg/kg), and methotrexate (0.5 mg/kg) during either discrete or cassette dosing, at a dose volume of 5 mL/kg. Blood samples were collected through the jugular vein and analyzed by liquid chromatography-tandem mass spectrometry. Pharmacokinetics parameters were calculated using Phoenix software version 8.1.

Results: Prednisolone significantly decreased the AUC0-last in both the arthritic group and the cassette group when compared to the standalone normal animal group. Neither cassette dosing in the normal group nor discrete dosing in the arthritic group affected the pharmacokinetics (PK) of diclofenac. However, the AUC0-last value for diclofenac significantly decreased during cassette dosing in the arthritic group. Individual administration of methotrexate in the arthritic group resulted in a significant decrease in AUC0-last, while the healthy group experienced a substantial increase when administered as a cassette.

Conclusion: Along with the pharmacological DDI, this study looked at how disease affected the PK of prednisolone, diclofenac, and methotrexate when these drugs were given in both discrete and cassette doses. Significant differences in AUC0-t and Cmax of prednisolone and methotrexate pharmacokinetics when dozed as a cassette or individually in arthritic groups were noticed. The serum concentration of methotrexate increased when it was combined with diclofenac. Further, the metabolism of methotrexate increased when combined with prednisolone.

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CiteScore
4.30
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