HEALTH - Institute for Biomedicine and Health Sciences, Joanneum Research Forschungsgesellschaft m.b.H., Graz, Austria.
Eur J Pharm Biopharm. 2012 Aug;81(3):635-41. doi: 10.1016/j.ejpb.2012.04.009. Epub 2012 Apr 24.
Methodologies for continuous sampling of lipophilic drugs and high-molecular solutes in the dermis are currently lacking. We investigated the feasibility of sampling a lipophilic topical drug and the locally released biomarker in the dermis of non-lesional and lesional skin of psoriatic patients over 25h by means of membrane-free dermal open-flow microperfusion probes (dOFM) and novel wearable multi-channel pumps.
Nine psoriatic patients received a topical p-38 inhibitor (BCT194, 0.5% cream) on a lesional and a non-lesional application site once daily for 8 days. Multiple dOFM sampling was performed for 25 h from each site on day 1 and day 8. Patients were mobile as dOFM probes were operated by a novel light-weight push-pull pump. Ultrasound was used to verify intradermal probe placement, cap-LC-MS/MS for BCT194 and ELISA for TNFα analysis.
dOFM was well tolerated and demonstrated significant drug concentrations in lesional as well as non-lesional skin after 8 days, but did not show significant differences between tissues. On day 8, TNFα release following probe insertion was significantly reduced compared to day 1.
Novel membrane-free probes and wearable multi-channel pumps allowed prolonged intradermal PK/PD profiling of a lipophilic topical drug in psoriatic patients. This initial study shows that dOFM overcomes limitations of microdialysis sampling methodology, and it demonstrates the potential for PK/PD studies of topical products and formulations in a clinical setting.
目前缺乏用于持续采集亲脂性药物和高分子溶质的真皮内样本的方法。我们通过无膜真皮开放式微流动探针（dOFM）和新型可穿戴多通道泵研究了在 25 小时内通过非病变和病变皮肤的真皮内对亲脂性局部药物和局部释放生物标志物进行采样的可行性。
9 例银屑病患者在病变和非病变部位每天接受一次局部 p38 抑制剂（BCT194，0.5%乳膏）治疗，共 8 天。第 1 天和第 8 天，每个部位进行 25 小时的多次 dOFM 采样。在新型轻量级推拉泵的操作下，患者可自由移动，以便进行 dOFM 探针操作。超声用于验证皮内探针位置，LC-MS/MS 用于 BCT194 分析，ELISA 用于 TNFα 分析。
dOFM 耐受性良好，在 8 天后在病变和非病变皮肤中均显示出显著的药物浓度，但在组织之间没有显著差异。与第 1 天相比，第 8 天探针插入后 TNFα 的释放明显减少。
新型无膜探针和可穿戴多通道泵允许对银屑病患者中亲脂性局部药物进行延长的皮内 PK/PD 分析。这项初步研究表明，dOFM 克服了微透析采样方法的局限性，并展示了在临床环境中对局部产品和制剂进行 PK/PD 研究的潜力。
