Fukasawa Takashi, Orii Takao, Tanaka Masayo, Suzuki Noriko, Kanzaki Yasushi
Pharmacy Department, Saiseikai Yokohamashi Nanbu Hospital, Yokohama, Japan.
Chem Pharm Bull (Tokyo). 2008 Aug;56(8):1177-80. doi: 10.1248/cpb.56.1177.
There are many reports that the drug-induced taste disorder is ascribable to the chelate reaction of a drug with zinc ion and the following zinc deficiency. As a quantitative measure of the chelating ability of drugs with zinc ions, the chelating ability was estimated from the electrode potential change of the Zn2+/Zn(Hg) system during the addition of a drug. The electrode potential was measured in a water-N,N-dimethylformamide mixed solution and in an aqueous solution depending on the solubility of the drugs. The observed electrode potential change showed a positive correlation to the frequency of the drug-induced taste disorder that was supplied from the manufacturer of the original drug. The regression analysis was carried out assuming that the frequency of the taste disorder and the electrode potential change was linear. The F-values, p-values, and R2-values were 4.29, 0.13, 0.589, and 4.15, 0.13, 0.580, respectively. The positive correlation between the drug-induced taste disorder and the electrode potential change appeared evident if the uncertainty in the frequency of the taste disorder was taken into consideration. Thus the assumption of the zinc ion chelating mechanism on the drug-induced disorder was also evident except for cisplatin. The frequency of the drug-induced taste disorder of bezafibrate was estimated to be 0.4--0.5 from the regression analysis.
有许多报道称，药物引起的味觉障碍可归因于药物与锌离子的螯合反应以及随后的锌缺乏。作为药物与锌离子螯合能力的定量指标，通过在添加药物过程中Zn2+/Zn(Hg)体系的电极电位变化来估算螯合能力。根据药物的溶解度，在水 - N,N - 二甲基甲酰胺混合溶液和水溶液中测量电极电位。观察到的电极电位变化与原药制造商提供的药物引起味觉障碍的频率呈正相关。假设味觉障碍频率与电极电位变化呈线性关系进行回归分析。F值、p值和R2值分别为4.29、0.13、0.589和4.15、0.13、0.580。如果考虑味觉障碍频率的不确定性，药物引起的味觉障碍与电极电位变化之间的正相关似乎很明显。因此，除顺铂外，药物引起的味觉障碍的锌离子螯合机制假设也很明显。通过回归分析估计，苯扎贝特引起的味觉障碍频率为0.4 - 0.5。
