Osman-Ponchet Hanan, Sevin Karine, Gaborit Alexandre, Wagner Nathalie, Poncet Michel
Galderma R&D, Les Templiers, 2400 Route des Colles, BP87, 06902, Sophia Antipolis, France.
Dermatol Ther (Heidelb). 2017 Mar;7(1):123-131. doi: 10.1007/s13555-016-0159-9. Epub 2016 Nov 30.
Adapalene 0.1%/benzoyl peroxide 2.5% (0.1% A/BPO) and adapalene 0.3%/BPO 2.5% (0.3% A/BPO) gels are fixed-combination options for the topical treatment of acne. However, the active compounds of these combinations are also available as monads, to be used in association or as monotherapy. These two in vitro studies determined the effect of different treatment regimens on the percutaneous absorption of adapalene (0.1% and 0.3%) gels and BPO 2.5% gel in ex vivo human skin.
In vitro percutaneous absorption studies were conducted using full-thickness human skin from six donors. Treatment regimens included the application of 0.1% A/BPO, 0.3% A/BPO, or four free-combination regimens of the monads. Skin samples were incubated for 24 h. Concentrations of adapalene and BPO equivalent (BPO-eq) (i.e. benzoic acid after chemical transformation of BPO) were measured using high-performance liquid chromatography. Comparison of regimens was performed using a bioequivalence criterion (estimated ratio bewteen 0.8 and 1.25).
The fixed combination 0.3% A/BPO regimen demonstrated more than three times higher absorption of adapalene versus the fixed-combination 0.1% A/BPO. Based on the bioequivalence acceptance criterion, all four free-combination regimens were different from 0.1% A/BPO and 0.3% A/BPO, with higher adapalene release delivered by the fixed combinations versus the free combinations. For BPO-eq, the results showed that the free-combination regimens where adapalene 0.1% was applied first were different from 0.1% A/BPO, with lower BPO-eq release delivered by these regimens compared to the fixed combination. The regimen adapalene 0.3% for 10 h followed by BPO 2.5% delivered lower BPO-eq release compared to the fixed combination.
The fixed-combination A/BPO gels provide optimal percutaneous absorption of the active compounds compared to free combinations of adapalene 0.1%, adapalene 0.3%, and BPO 2.5%. The higher concentration of adapalene in the 0.3% A/BPO gel and the resulting higher absorption may explain higher clinical efficacy.
阿达帕林0.1%/过氧化苯甲酰2.5%（0.1%A/BPO）凝胶和阿达帕林0.3%/BPO 2.5%（0.3%A/BPO）凝胶是用于痤疮局部治疗的固定复方制剂。然而，这些复方制剂中的活性成分也有单一制剂形式，可联合使用或作为单一疗法使用。这两项体外研究确定了不同治疗方案对阿达帕林（0.1%和0.3%）凝胶和BPO 2.5%凝胶在离体人皮肤中经皮吸收的影响。
使用来自六名供体的全层人皮肤进行体外经皮吸收研究。治疗方案包括应用0.1%A/BPO、0.3%A/BPO或四种单一制剂的自由联合方案。皮肤样本孵育24小时。使用高效液相色谱法测量阿达帕林和BPO当量（BPO-eq）（即BPO化学转化后的苯甲酸）的浓度。使用生物等效性标准（估计比值在0.8至1.25之间）对各方案进行比较。
固定复方0.3%A/BPO方案中阿达帕林的吸收比固定复方0.1%A/BPO高两倍多。根据生物等效性接受标准，所有四种自由联合方案均与0.1%A/BPO和0.3%A/BPO不同，固定复方制剂比自由联合制剂释放出更高的阿达帕林。对于BPO-eq，结果表明，先应用0.1%阿达帕林的自由联合方案与0.1%A/BPO不同，这些方案释放的BPO-eq比固定复方制剂低。与固定复方制剂相比，先应用0.3%阿达帕林10小时后再应用2.5%BPO的方案释放的BPO-eq较低。
与0.1%阿达帕林、0.3%阿达帕林和2.5%BPO的自由联合制剂相比，固定复方A/BPO凝胶能使活性成分实现最佳经皮吸收。0.3%A/BPO凝胶中较高浓度的阿达帕林及其导致的更高吸收可能解释了更高的临床疗效。
