Enhancement of the 1-Octanol/Water Partition Coefficient of the Anti-Inflammatory Indomethacin in the Presence of Lidocaine and Other Local Anesthetics

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• 作者：Ryo Tateuchi ; Naoki Sagawa ; Yohsuke Shimada ; Satoru Goto
• 刊名：Journal of Physical Chemistry B
• 出版年：2015
• 出版时间：July 30, 2015
• 年：2015
• 卷：119
• 期：30
• 页码：9868-9873
• 全文大小：321K
• ISSN：1520-5207

文摘

Side effects and excessive potentiation of drug efficacy caused by polypharmacy are becoming important social issues. The apparent partition coefficient of indomethacin (log P鈥?sub>IND) increases in the presence of lidocaine, and this is used as a physicochemical model for investigating polypharmacy. We examined the changes in log P鈥?sub>IND caused by clinically used local anesthetics鈥攍idocaine, tetracaine, mepivacaine, bupivacaine, and dibucaine鈥攁nd by structurally similar basic drugs鈥攑rocainamide, imipramine, and diltiazem. The quantitative structure鈥揳ctivity relationship study of log P鈥?sub>IND showed that the partition coefficient values (log P_LA) and the structural entropic terms (螖S_obs, log f) of the additives affect log P鈥?sub>IND. These results indicate that the local anesthetics and structurally similar drugs function as phase-transfer catalysts, increasing the membrane permeability of indomethacin via heterogeneous intermolecular association. Therefore, we expect that the potency of indomethacin, an acidic nonsteroidal anti-inflammatory drug, will be increased by concurrent administration of the other drugs.