Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
Molecules. 2012 Jan 5;17(1):480-91. doi: 10.3390/molecules17010480.
The permeation properties of twenty newly synthesized α-alkoxyalkanoyl and α-aryloxyalkanoyl C-21 esters of standard corticosteroids: Fluocinolone acetonide, dexamethasone, triamcinolone acetonide and hydrocortisone were established using a PAMPA assay (70% silicone oil and 30% isopropyl myristate). The data were compared with parent corticosteroids with addition of mometasone furoate and hydrocortisone acetate. All newly synthesized corticosteroid C-21 esters have effective permeability coefficients higher then -6, mostly followed with high values of retention factors and low permeation. The examined compounds were grouped through relationship between obtained retention factors and permeation parameters (groups I-III). The classification confirmed group I (membrane retentions as well as permeation lower then 30%) for all corticosteroid standards except mometasone furoate, a potent topical corticosteroid which, with high membrane retention (81%) and low permeation (7.7%) fits into group III. The largest number of new synthesized corticosteroids C-21 esters, among them all fluocinolone acetonide C-21 esters, have high membrane retentions (32.4%-86.5%) and low permeations (1.3%-27.1%), fitting in group III. The classification was related to previously obtained anti-inflammatory activity data for the fluocinolone acetonide C-21 esters series. According to the PAMPA results the new synthesized esters could be considered as potential new prodrugs with useful benefit/risk ratio.
二十种新合成的标准皮质甾类药物的 α-烷氧基烷酰基和 α-芳氧基烷酰基 C-21 酯的渗透特性：氟轻松丙酮、地塞米松、曲安奈德丙酮和氢化可的松，采用 PAMPA 测定法（70%硅酮油和 30%肉豆蔻异丙酯）进行了研究。将所得数据与母体皮质甾类药物进行了比较，其中加入了莫米松糠酸酯和醋酸氢化可的松。所有新合成的皮质甾酮 C-21 酯的有效渗透系数均高于-6，大多数保留因子和低渗透值都很高。通过获得的保留因子和渗透参数之间的关系（组 I-III）对所研究的化合物进行了分组。分类证实了所有皮质甾类药物标准品（除莫米松糠酸酯外）均属于 I 组（膜保留和渗透均低于 30%），莫米松糠酸酯是一种强效局部皮质甾类药物，具有高膜保留（81%）和低渗透（7.7%），因此属于 III 组。新合成的皮质甾酮 C-21 酯中，有许多具有高膜保留（32.4%-86.5%）和低渗透（1.3%-27.1%），属于 III 组，其中包括所有的氟轻松丙酮 C-21 酯。根据 PAMPA 结果，新合成的酯类可被认为是具有潜在应用价值的新型前药，具有良好的收益/风险比。
