Custódio J B, Almeida L M, Madeira V M
Laboratório de Bioquímica, Faculdade de Farmácia, Combra, Portugal.
Biochem Biophys Res Commun. 1991 May 15;176(3):1079-85. doi: 10.1016/0006-291x(91)90394-m.
A direct method using derivative spectrophotometry was developed for determining membrane-water molar partition coefficients (Kp) of the anticancer drugs tamoxifen (TAM) and 4-hydroxytamoxifen (OHTAM). This method explores a shift in the absorption spectra of the drugs when removed from the aqueous phase to a hydrophobic environment. Partition of TAM and OHTAM depends on membrane composition and on drug concentration, temperature and presence of cholesterol. Unlike OHTAM, partition of TAM in DMPC bilayers, liposomes of sarcoplasmic reticulum (SR) lipids and native membranes of SR and mitochondria decreases linearly with drug concentration. Additionally, the partition of these drugs is higher in SR native membranes than in liposomes of SR lipids. The partition also depends on membrane type, being higher in mitochondria than in SR membranes. Maximal partitionings in DMPC are observed at temperatures in the range of the main phase transition. Cholesterol strongly affects the incorporation of drugs and maximal inhibition was observed in DMPC bilayers.
开发了一种使用导数分光光度法的直接方法来测定抗癌药物他莫昔芬（TAM）和4-羟基他莫昔芬（OHTAM）的膜-水摩尔分配系数（Kp）。该方法探索了药物从水相转移到疏水环境时吸收光谱的变化。TAM和OHTAM的分配取决于膜组成、药物浓度、温度以及胆固醇的存在。与OHTAM不同，TAM在二肉豆蔻酰磷脂酰胆碱（DMPC）双层膜、肌浆网（SR）脂质体以及SR和线粒体的天然膜中的分配随药物浓度呈线性下降。此外，这些药物在SR天然膜中的分配高于在SR脂质体中的分配。分配还取决于膜类型，在线粒体中比在SR膜中更高。在主相变温度范围内观察到DMPC中的最大分配。胆固醇强烈影响药物的掺入，并且在DMPC双层膜中观察到最大抑制作用。
