Mechanism of Indomethacin Partition between n-Octanol and Water
Mechanism of Indomethacin Partition between n-Octanol and Water
复制标题
吲哚美辛正辛醇与水的分配机理
DOI：
10.1248/cpb.29.2330
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
H. Terada
中科院分区：
文献类型：
--
作者：
T. Inagi;T. Muramatsu;H. Nagai;H. Terada
为了研究吲哚美辛（indomethacin，LND）向生物膜转移的基本过程，在25°C下，采用摇瓶法测定了不同pH值和不同阳离子存在下，LND在正辛醇和水之间的分配系数。表观分配系数随pH值的升高而降低，非离子化IND的真实分配系数为1.20× 10 ~（-4），离子化IND的真实分配系数为1.72×10 ~（-1）。IND阴离子被发现很容易被转移到疏水区形成离子对配合物与阳离子在水相中。IND与铵离子形成的离子对络合物比与钠、钾离子形成的离子对络合物更容易转移到有机相中。在这项研究中，在碱性pH值的不稳定的药物的离子对分配的定量分析方法建立在两个以上的阳离子物种存在的条件下。
To examine the fundamental process of the transfer of indomethacin (LND) to the biological membrane, the partition coefficient between n-octanol and water was measured at various pH values or in the presence of various cations by the shaking-flask method at 25°C. The apparent partition coefficient decreased with increase in pH and the true partition coefficient of unionized IND was determined to be 1.20×104, while that of ionized IND was 1.72×10-1. The IND anion was found to be readily transferred to the hydrophobic region by forming ion-pair complexes with cations in the aqueous phase. The ion-pair complex of IND with the ammonium ion was transferred to the organic phase more readily than that with the sodium or potassiumion. In this study, a method for quantitative analysis of the ion-pair partition of an unstable drug at alkaline pH was established under conditions where more than two cationic species were present.