Tigka E, Daskala I, Rallis G, Anagnostopoulou S, Tesseromatis C
Department of Pharmacology, Medical School, University of Athens, Athens, Greece.
Eur J Drug Metab Pharmacokinet. 2005 Oct-Dec;30(4):235-41. doi: 10.1007/BF03190626.
Adjuvant arthritis, as a model for investigating rheumatoid arthritis (RA), is characterized by reduced plasma albumin levels and interferes with drug binding in the plasma and tissues (liver and bone). Ampicillin interacts with non-steroidal anti-inflammatory drugs (NSAIDs) due to the acidic pk(a). The aim of this study was to investigate in vitro the concentrations of ampicillin in the serum, femur, mandible and liver proteins following the co-administration of ketoprofen, flurbiprofen, ibuprofen, oxyphenbutazone and ASA in adjuvant arthritis versus healthy control rats. Ampicillin binding was found to be reduced in the serum of arthritic rats, and ampicillin binding to serum proteins was also reduced under the influence of NSAIDs in the control animals. Differences in ampicillin binding were observed in the various tissues due to the effect of adjuvant arthritis as well as that due to the co-administration of NSAIDs. In conclusion, this in vitro study may provide a plausible explanation for the ampicillin-NSAIDs interaction and such a finding may be of therapeutic significance in the treatment of painful arthritic disease such as RA.
佐剂性关节炎作为研究类风湿性关节炎(RA)的一种模型,其特征是血浆白蛋白水平降低,并干扰药物在血浆及组织(肝脏和骨骼)中的结合。氨苄西林由于其酸性解离常数(pKa),会与非甾体抗炎药(NSAIDs)发生相互作用。本研究的目的是在体外研究,在佐剂性关节炎大鼠与健康对照大鼠中,联合给予酮洛芬、氟比洛芬、布洛芬、羟基保泰松和阿司匹林后,血清、股骨、下颌骨及肝脏蛋白中氨苄西林的浓度。研究发现,关节炎大鼠血清中氨苄西林的结合减少,并且在对照动物中,非甾体抗炎药的影响下,氨苄西林与血清蛋白的结合也减少。由于佐剂性关节炎的影响以及非甾体抗炎药联合给药的影响,在不同组织中观察到了氨苄西林结合的差异。总之,这项体外研究可能为氨苄西林 - 非甾体抗炎药的相互作用提供一个合理的解释,并且这样的发现可能对治疗诸如类风湿性关节炎等疼痛性关节炎疾病具有治疗意义。