Skin penetration and tissue permeation after topical administration of diclofenac

<b>Objective:</b> Topical delivery of drugs is an alternative to oral administration, often with similar efficacy but potentially a more favorable tolerability profile. However, topical formulations need to be able to penetrate the skin and permeate to the target areas in quantities sufficient to exert a therapeutic effect. Many factors can affect this process, including the physicochemical properties of the drug, the formulation used, and the site and mode of application. It is believed that measurement of drug concentrations at the sites of action may be an indicator of their likely efficacy. This review addresses these issues, with reference to topically administered diclofenac in osteoarthritis. <b>Methods:</b> Articles relevant to this review were identified after a systematic search of Medline and Embase, using the key words “diclofenac”, "topical administration" and “osteoarthritis” in the search strategy. <b>Results:</b> The sparse data available indicate that topical diclofenac can penetrate and permeate to deeper tissues, with a lower plasma to tissue ratio than oral diclofenac. The tissue diclofenac levels after topical delivery are sustained over time (at least several hours). However, there is not enough data to establish how diclofenac levels in the joint compare with IC₅₀ levels (50% of the maximum inhibition of prostaglandin synthesis) established following oral administration. <b>Conclusions:</b> After topical application, diclofenac can penetrate the skin and permeate to deeper tissues, where it reaches a concentration that appears to be sufficient to exert a therapeutic effect. More robust methods are required for in vivo characterization to better estimate the clinical efficacy of topically applied drugs.

<b>研究目的：</b>药物经皮给药是口服给药的替代方案，通常疗效相当，但耐受性表现可能更优。然而，经皮制剂需能够穿透皮肤，并以足够剂量渗透至靶部位以发挥治疗作用。诸多因素可影响该过程，包括药物的理化性质、所用制剂、给药部位与给药方式。有观点认为，对作用部位的药物浓度进行检测，或可作为其潜在疗效的指标。本综述围绕上述问题展开论述，并以骨关节炎患者经皮给药的双氯芬酸（diclofenac）为例进行探讨。<b>研究方法：</b>本综述通过对Medline与Embase数据库进行系统检索，以“双氯芬酸（diclofenac）”、“经皮给药（topical administration）”及“骨关节炎（osteoarthritis）”为关键词构建检索策略，筛选得到相关文献。<b>研究结果：</b>现有零散数据表明，经皮给予双氯芬酸可穿透皮肤并渗透至深层组织，其血浆与组织浓度之比低于口服双氯芬酸。经皮给药后，组织内双氯芬酸浓度可维持一段时间（至少数小时）。然而，目前尚无足够数据明确，关节内双氯芬酸浓度与口服给药后测得的半数抑制浓度（IC₅₀，即前列腺素合成最大抑制率达50%时的浓度）水平对比情况如何。<b>研究结论：</b>经皮给药后，双氯芬酸可穿透皮肤并渗透至深层组织，其浓度足以发挥治疗作用。目前仍需更可靠的体内表征方法，以更准确地评估经皮给药药物的临床疗效。