Differentiated in vivo skin penetration of salicylic compounds in hairless rats measured by cutaneous microdialysis
Differentiated in vivo skin penetration of salicylic compounds in hairless rats measured by cutaneous microdialysis
复制标题
DOI：
10.1016/j.ejps.2003.11.004
复制
发表时间：
2004-02-01
影响因子：
4.6
通讯作者：
Groth, L
中科院分区：
文献类型：
--
作者：
Simonsen, L;Jorgensen, A;Groth, L
目的是调查在体内皮肤渗透的四个C-14-水杨酸化合物使用微透析和皮肤浓度的结构特征。此外，比较两种体内后透析回收方法，以估计真实的未结合细胞外浓度。将微透析探针插入无毛大鼠的真皮中。局部应用等摩尔的C-14-水杨酸制剂，并连续采集透析液4 h。通过药物法（C-14-水杨酸化合物本身）和校准品法（H-3-水杨酸作为内标物）通过后透析估计真实细胞外浓度。通过超声扫描测量探针深度。在应用C-14-水杨酰胺（低蛋白结合）和亲脂酯C-14-水杨酸丁酯（在皮肤扩散过程中完全水解为C-14-水杨酸）后，发现皮肤浓度较高。蛋白质结合和解离可以分别解释C-14-水杨酸和C-14-水杨酸二乙胺的较低真皮浓度。穿刺针深度对透析液浓度无显著影响。两种体内回收率校正方法均未降低浓度-时间曲线的变异。总之，发现不同的渗透动力学排序：C-14-水杨酰胺大于或等于C-14-水杨酸丁酯> C-14-水杨酸> C-14-水杨酸二乙胺。皮肤浓度与模型化合物的结构特征有关。两种校正方法的性能相似;然而，校准品方法具有在实验期间用作质量控制的优势。(C)2003 Elsevier B. V.保留所有权利。
The purpose was to investigate the in vivo skin penetration of four C-14-salicylic compounds using microdialysis and to relate dermal concentrations to structural features. Furthermore, to compare two in vivo retrodialysis recovery methods for estimation of true unbound extracellular concentrations. Microdialysis probes were inserted in the dermis of hairless rats. Equimolal C-14-salicylic formulations were applied topically and dialysate sampled consecutively for 4 h. True extracellular concentrations were estimated by retrodialysis by drug method (the C-14-salicylic compounds themselves) and by retrodialysis by calibrator method (H-3-salicylic acid as internal standard). Probe depth was measured by ultrasound scanning. High dermal concentrations were found after application of C-14-salicylamide (low protein-binding) and the lipophilic ester C-14-butyl salicylate, which was completely hydrolysed to C-14-salicylic acid during skin diffusion. Protein binding and dissociation may explain the lower dermal concentrations of C-14-salicylic acid and C-14-diethylamine salicylate, respectively. Probe depth did not significantly influence dialysate concentrations. The two in vivo recovery correction methods did not reduce the variation in concentration-time curves. In conclusion, differentiated penetration kinetics was found ranking: C-14-salicylamide greater than or equal to C-14-butyl salicylate > C-14-salicylic acid > C-14-diethylamine salicylate. Dermal concentrations were related to structural features of the model compounds. The two correction methods performed alike; however, the calibrator method has the advantage of serving as a quality control during experiments. (C) 2003 Elsevier B.V. All rights reserved.