Huang C H, Kimura R, Bawarshi-Nassar R, Hussain A
J Pharm Sci. 1985 Dec;74(12):1298-301. doi: 10.1002/jps.2600741210.
The nasal absorption of L-tyrosine and the effect of structural modification on that absorption have been studied using an in-situ experimental technique. The extent of nasal absorption of the amino acid was found to be the same at pH values of 4.0 and 7.4 but dependent on concentration in the range of 2.8 X 10(-4)-2.2 X 10(-3) M. O-Acyl-L-tyrosine esters, although possessing higher octanol-water (pH 7.4) partition coefficients, have the same rate of nasal absorption as the parent amino acid. N-Acetyl-L-tyrosine, on the other hand, was found to have both partition coefficient and nasal absorption rate similar to those of L-tyrosine. Esterification of the carboxyl moiety of L-tyrosine results in derivatives that hydrolyze in the in-situ perfusion medium generating the original amino acid. The rate of nasal absorption of these derivatives was, therefore, determined from an overall disappearance rate which accounted for the rate of hydrolysis to L-tyrosine. These carboxylic esters were absorbed 4 to 10 times faster than L-tyrosine. Although the carboxylic esters of L-tyrosine possess higher octanol-water partition coefficients than the parent amino acid, the differences in the rates of nasal absorption could not be attributed solely to partition coefficient. The enhancement in the rate of absorption observed for these esters was attributed instead to the absence of the negative charge on the carboxylate moiety. It is a result of this negative charge that the rates of nasal absorption of L-tyrosine, O-acyl-L-tyrosine esters and N-acetyl-L-tyrosine are similar, despite significant differences in their partition coefficients.
采用原位实验技术研究了L-酪氨酸的鼻腔吸收以及结构修饰对该吸收的影响。发现该氨基酸在pH值为4.0和7.4时的鼻腔吸收程度相同，但在2.8×10⁻⁴ - 2.2×10⁻³ M范围内依赖于浓度。O-酰基-L-酪氨酸酯虽然具有更高的正辛醇-水（pH 7.4）分配系数，但其鼻腔吸收速率与母体氨基酸相同。另一方面，发现N-乙酰-L-酪氨酸的分配系数和鼻腔吸收速率与L-酪氨酸相似。L-酪氨酸羧基部分的酯化产生在原位灌注介质中水解生成原始氨基酸的衍生物。因此，这些衍生物的鼻腔吸收速率由考虑到水解为L-酪氨酸速率的总体消失速率确定。这些羧酸酯的吸收速度比L-酪氨酸快4至10倍。尽管L-酪氨酸的羧酸酯比母体氨基酸具有更高的正辛醇-水分配系数，但鼻腔吸收速率的差异不能仅归因于分配系数。相反，观察到这些酯吸收速率的提高归因于羧酸根基团上不存在负电荷。正是由于这种负电荷，L-酪氨酸、O-酰基-L-酪氨酸酯和N-乙酰-L-酪氨酸的鼻腔吸收速率相似，尽管它们的分配系数存在显著差异。
