Takahashi K, Murakami T, Kamata A, Yumoto R, Higashi Y, Yata N
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
Pharm Res. 1994 Mar;11(3):388-92. doi: 10.1023/a:1018908903475.
The enhancing action of decanoic acid (C10) and its derivatives on mucosal absorption of phenolsulfonphthalein (PSP) in the jejunum or colon was analyzed using pharmacokinetics in rats. After administration of a solution containing PSP and an enhancer [C10, 2-hydroxydecanoic acid (2-OHC10), or 3-hydroxydecanoic acid (3-OHC10)] into the jejunal or colonic loop, the amounts of PSP and enhancer remaining in the loop and/or plasma PSP concentration were determined periodically. 2-OHC10 exhibited a greater absorption enhancing potency than C10, while 3-OHC10 was less effective. Disappearance of residual PSP from the loop ceased after complete absorption of the enhancer. The enhancer-induced disappearance rate constant of PSP correlated well with the product of the enhancer disappearance rate and its capacity to sequester calcium ions. In conclusion, the enhancement of PSP mucosal absorption by C10 and its derivatives is consistent with a pharmacokinetic model, assuming that the enhanced membrane permeability of PSP depends on the enhancer disappearance kinetics from the loop and its calcium ion sequestration capacity.
利用大鼠的药代动力学分析了癸酸（C10）及其衍生物对空肠或结肠中酚磺酞（PSP）黏膜吸收的增强作用。将含有PSP和增强剂[C10、2-羟基癸酸（2-OHC10）或3-羟基癸酸（3-OHC10）]的溶液注入空肠或结肠肠袢后，定期测定肠袢中剩余的PSP和增强剂的量以及血浆PSP浓度。2-OHC10表现出比C10更强的吸收增强效力，而3-OHC10的效果较差。增强剂完全吸收后，肠袢中残留PSP的消失停止。增强剂诱导的PSP消失速率常数与增强剂消失速率及其螯合钙离子能力的乘积密切相关。总之，C10及其衍生物对PSP黏膜吸收的增强作用与药代动力学模型一致，假设PSP膜通透性的增强取决于增强剂从肠袢中的消失动力学及其钙离子螯合能力。
