Ault J M, Lunte C E, Meltzer N M, Riley C M
Department of Pharmaceutical Chemistry, University of Kansas, Lawrence 66045.
Pharm Res. 1992 Oct;9(10):1256-61. doi: 10.1023/a:1015892914649.
Microdialysis perfusion in vivo has the potential to be a powerful sampling technique in dermal and transdermal drug delivery studies. Characterization of a commercially available microdialysis probe in vitro considering relevant physiological parameters is a vital first step in the evaluation of microdialysis as a dermal sampling technique. In previous microdialysis studies, analyte concentration and neutrality have been implicated in altering microdialysis recovery. The recovery of a model compound 5-fluorouracil (5-FU) was investigated at several pH values and donor concentrations. The relative recovery of 5-FU by the microdialysis probe was affected by pH but not by donor concentration. To confirm further that the changing concentration and pH profile presented by the flux of 5-FU was not significantly altering microdialysis recovery, an experiment comparing direct and microdialysis sampling of a Franz diffusion cell receptor compartment was performed. Although the 5-FU concentration (0-686 ng/ml) and pH (7.40-7.24) changed substantially, the recovery of 5-FU was not adversely affected. To demonstrate the feasibility of dermal microdialysis, the flux of a commercial preparation of 5-fluorouracil was monitored utilizing a microdialysis probe implanted in excised rat skin in vitro. The results from the dermally implanted probe demonstrate the potential of the technique while establishing the limitations of the current microdialysis system.
体内微透析灌注有潜力成为皮肤和经皮给药研究中一种强大的采样技术。在体外考虑相关生理参数对市售微透析探针进行表征,是评估微透析作为一种皮肤采样技术的至关重要的第一步。在以往的微透析研究中,分析物浓度和酸碱度被认为与改变微透析回收率有关。在几个酸碱度值和供体浓度下研究了模型化合物5-氟尿嘧啶(5-FU)的回收率。微透析探针对5-FU的相对回收率受酸碱度影响,但不受供体浓度影响。为了进一步证实5-FU通量所呈现的浓度和酸碱度变化曲线不会显著改变微透析回收率,进行了一项比较Franz扩散池受体隔室直接采样和微透析采样的实验。尽管5-FU浓度(0 - 686纳克/毫升)和酸碱度(7.40 - 7.24)发生了显著变化,但5-FU的回收率并未受到不利影响。为了证明皮肤微透析的可行性,利用植入体外切除大鼠皮肤中的微透析探针监测了一种5-氟尿嘧啶商业制剂的通量。皮肤植入探针的结果展示了该技术的潜力,同时也确定了当前微透析系统的局限性。