Skin Pharmacokinetics of Transdermal Scopolamine: Measurements and Modeling
Skin Pharmacokinetics of Transdermal Scopolamine: Measurements and Modeling
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DOI：
10.1021/acs.molpharmaceut.1c00238
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发表时间：
2021-06-14
影响因子：
4.9
通讯作者：
Delgado-Charro, M. Begona
中科院分区：
文献类型：
--
作者：
Pensado, Andrea;Hattam, Laura;Delgado-Charro, M. Begona
预测局部制剂的皮肤吸收和局部生物利用度仍然是一项艰巨的任务。预测局部生物利用度的一个重要挑战是关于局部药物产品应用后局部和全身药物浓度的可用信息有限。市售透皮贴剂，如Scopoderm（Novartis Consumer Health UK），提供了测试这些实验方法的机会，因为全身药代动力学数据可用于验证预测模型。因此，长期的研究目标是开发一种基于生理学的药代动力学模型（PBPK），以预测复杂皮肤病产品中活性物质的皮肤吸收和处置。这项工作探讨了体外释放和皮肤渗透试验（分别为IVRT和IVPT），以及体外和体内角质层（SC）和活组织（VT）采样数据，是否可以提供一个令人满意的描述药物“输入率”进入皮肤，随后进入体循环。东莨菪碱的体外释放和皮肤渗透结果与先前报道的所研究的市售贴剂的性能一致。东莨菪碱的皮肤药理学（DPK）的新皮肤采样数据也准确地反映了从贴剂粘合剂中快速递送“预充”剂量，叠加在从药物储库中较慢的速率控制输入上。体外和体内SC和VT皮肤隔室中的东莨菪碱浓度-时间曲线，以及IVRT释放和IVPT渗透动力学，反映了Scopoderm透皮贴剂的输入速率和药物递送质量标准，并揭示了皮肤结合对局部药物分布的重要性。进一步的数据分析和皮肤PK建模表明，进一步完善和发展概述的方法。
Prediction of skin absorption and local bioavailability from topical formulations remains a difficult task. An important challenge in forecasting topical bioavailability is the limited information available about local and systemic drug concentrations post application of topical drug products. Commercially available transdermal patches, such as Scopoderm (Novartis Consumer Health UK), offer an opportunity to test these experimental approaches as systemic pharmacokinetic data are available with which to validate a predictive model. The longterm research aim, therefore, is to develop a physiologically based pharmacokinetic model (PBPK) to predict the dermal absorption and disposition of actives included in complex dermatological products. This work explored whether in vitro release and skin permeation tests (IVRT and IVPT, respectively), and in vitro and in vivo stratum corneum (SC) and viable tissue (VT) sampling data, can provide a satisfactory description of drug "input rate" into the skin and subsequently into the systemic circulation. In vitro release and skin permeation results for scopolamine were consistent with the previously reported performance of the commercial patch investigated. New skin sampling data on the dermatopharmacokinetics (DPK) of scopolamine also accurately reflected the rapid delivery of a "priming" dose from the patch adhesive, superimposed on a slower, rate-controlled input from the drug reservoir. The scopolamine concentration versus time profiles in SC and VT skin compartments, in vitro and in vivo, taken together with IVRT release and IVPT penetration kinetics, reflect the input rate and drug delivery specifications of the Scopoderm transdermal patch and reveal the importance of skin binding with respect to local drug disposition. Further data analysis and skin PK modeling are indicated to further refine and develop the approach outlined.