Hashimoto Y, Murakami T, Kumasa C, Higashi Y, Yata N, Takano M
Institute of Pharmaceutical Sciences, Hiroshima University School of Medicine, Japan.
J Pharm Pharmacol. 1998 Jun;50(6):621-6. doi: 10.1111/j.2042-7158.1998.tb06895.x.
To estimate the absolute concentration of substrates surrounding a microdialysis probe in-vivo, we developed a simple calibration method using endogenous glucose as an internal recovery marker and determined the skin distribution of tranilast (N-(3,4-dimethoxy-cinnamoyl)anthranic acid), an anti-allergic agent, in rats. This calibration method was based on the assumption that the concentration of glucose in the extracellular fluid of skin tissues is the same as that in plasma and that the in-vivo recovery ratio of glucose to tranilast by microdialysis is the same as that estimated in-vitro. Based on these assumptions, the dialysate concentrations of tranilast and glucose recovered from cutaneous microdialysis, glucose concentration in plasma, and in-vitro recovery ratio of tranilast to glucose by microdialysis were determined for the estimation of absolute unbound concentration of tranilast in the extracellular fluid of skin tissues. In an in-vitro study employing plasma containing tranilast, the unbound concentration of tranilast in plasma estimated from the dialysate concentration was just comparable with that determined by ultrafiltration methods. Also in an in-vivo study under steady-state plasma concentration of tranilast in rats, the estimated concentration of tranilast in the skin extracellular fluid was the same level as the unbound concentration of tranilast in plasma. Using the present calibration method, the skin distribution of tranilast administered into the intestinal loop or transdermally was continuously monitored in a quantitative manner.
为了在体内估计围绕微透析探针的底物的绝对浓度，我们开发了一种简单的校准方法，使用内源性葡萄糖作为内部回收率标记物，并确定了抗过敏剂曲尼司特（N-(3,4-二甲氧基肉桂酰基)邻氨基苯甲酸）在大鼠体内的皮肤分布。该校准方法基于以下假设：皮肤组织细胞外液中的葡萄糖浓度与血浆中的相同，并且微透析对葡萄糖和曲尼司特的体内回收率与体外估计的相同。基于这些假设，测定了从皮肤微透析中回收的曲尼司特和葡萄糖的透析液浓度、血浆中的葡萄糖浓度以及微透析对曲尼司特与葡萄糖的体外回收率，以估计皮肤组织细胞外液中曲尼司特的绝对游离浓度。在一项使用含曲尼司特血浆的体外研究中，根据透析液浓度估计的血浆中曲尼司特的游离浓度与通过超滤法测定的浓度相当。同样在大鼠曲尼司特稳态血浆浓度下的体内研究中，皮肤细胞外液中曲尼司特的估计浓度与血浆中曲尼司特的游离浓度处于同一水平。使用本校准方法，以定量方式连续监测了经肠环给药或经皮给药的曲尼司特在皮肤中的分布。
