title: Enhancement of the 1-Octanol/Water Partition Coefficient of the Anti-Inflammatory Indomethacin in the Presence of Lidocaine and Other Local Anesthetics.
abstract: Side effects and excessive potentiation of drug efficacy caused by polypharmacy are becoming important social issues. The apparent partition coefficient of indomethacin (log P'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'IND caused by clinically used local anesthetics-lidocaine, tetracaine, mepivacaine, bupivacaine, and dibucaine-and by structurally similar basic drugs-procainamide, imipramine, and diltiazem. The quantitative structure-activity relationship study of log P'IND showed that the partition coefficient values (log PLA) and the structural entropic terms (ΔSobs, log f) of the additives affect log P'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.
authors.affiliation: †Faculty of Pharmaceutical Sciences, ‡Center for Drug Delivery Research, §Center for Physical Pharmaceutics, Research Institute for Science and Technology, and ∥Division of Colloid and Interface Science Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Tateuchi
authors.affiliation: †Faculty of Pharmaceutical Sciences, ‡Center for Drug Delivery Research, §Center for Physical Pharmaceutics, Research Institute for Science and Technology, and ∥Division of Colloid and Interface Science Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Sagawa
authors.affiliation: †Faculty of Pharmaceutical Sciences, ‡Center for Drug Delivery Research, §Center for Physical Pharmaceutics, Research Institute for Science and Technology, and ∥Division of Colloid and Interface Science Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Yohsuke
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: †Faculty of Pharmaceutical Sciences, ‡Center for Drug Delivery Research, §Center for Physical Pharmaceutics, Research Institute for Science and Technology, and ∥Division of Colloid and Interface Science Research Institute for Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Goto
mesh_terms: D020003:1-Octanol / Q000737:chemistry*; D000779:Anesthetics, Local / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D019277:Entropy; D007213:Indomethacin / Q000737:chemistry*; D008012:Lidocaine / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D000779:Anesthetics, Local; D000893:Anti-Inflammatory Agents; D014867:Water; D008012:Lidocaine; D020003:1-Octanol; D007213:Indomethacin