Modamio P, Lastra C F, Mariño E L
Department of Pharmacy and Pharmaceutical Technology, Clinical Pharmacy and Pharmacotherapy Unit, Faculty of Pharmacy, University of Barcelona, Avda. Joan XXIII s/n, 08028, Barcelona, Spain.
Int J Pharm. 2000 Jan 25;194(2):249-59. doi: 10.1016/s0378-5173(99)00380-4.
In vitro diffusion experiments with propranolol, oxprenolol, metoprolol and atenolol were carried out using excised human abdominal skin. The main permeation parameters (permeability coefficient, flow and lag time) were calculated and compared as measurement of intrinsic permeability across human skin. A long lag time and a low steady-state flow were found for all drugs assayed. Skin permeability predicted at steady state did not reach therapeutic concentrations, which indicated the need for appropriate chemical penetration enhancers or vehicles to overcome limiting factors. The results, including those of celiprolol and bisoprolol reported previously, correlated with physicochemical properties, especially with lipophilicity, one of the main factors in drug permeability prediction through human skin.
使用切除的人体腹部皮肤进行了普萘洛尔、氧烯洛尔、美托洛尔和阿替洛尔的体外扩散实验。计算并比较了主要渗透参数（渗透系数、流量和滞后时间），作为衡量药物经人体皮肤固有渗透性的指标。在所测定的所有药物中均发现较长的滞后时间和较低的稳态流量。稳态下预测的皮肤渗透性未达到治疗浓度，这表明需要合适的化学渗透促进剂或载体来克服限制因素。包括先前报道的塞利洛尔和比索洛尔的结果在内，这些结果与物理化学性质相关，特别是与亲脂性相关，亲脂性是预测药物经人体皮肤渗透性的主要因素之一。
