Biofrontera Bioscience GmbH, Leverkusen, Germany.
DermResearch Inc., Austin, Texas, USA.
Clin Pharmacol Drug Dev. 2022 Apr;11(4):535-550. doi: 10.1002/cpdd.1023. Epub 2021 Oct 11.
The nanoemulsion-based 10% aminolevulinic acid (ALA) hydrochloride gel BF-200 ALA optimizes epidermal penetration of its active ingredient and is approved for topical photodynamic therapy (PDT) for the treatment of actinic keratosis in the United States and Europe. To characterize systemic absorption from dermal application during PDT, ALA and its key active metabolite protoporphyrin IX (PpIX) were analyzed in 2 maximal usage pharmacokinetic trials (MUsT) in patients severely affected with actinic keratosis. The primary objective of both MUsTs was to assess baseline-adjusted plasma concentration-time curves for ALA and PpIX after a single PDT treatment applying either 2 g (1 tube) of BF-200 ALA on the face (MUsT-1) or applying 6 g (3 tubes) of BF-200 ALA on the face/scalp or body periphery (MUsT-2), to 20 or 60 cm , respectively. All PDTs were performed using red light at around 635 nm wavelength. Safety and tolerability were documented along with pharmacokinetics. In both MUsTs, ALA plasma concentrations were transiently increased to a maximum concentration at about 2.5 to 3.3 times above endogenous baseline with time to maximum concentration at ≈3 hours after dosing. Plasma levels subsequently returned to baseline within 10 hours after dosing. Overall baseline-adjusted mean area under the baseline-adjusted plasma concentration-time curve from time zero to the last sampling time point at which the concentration was at or above the lower limit of quantification ranged from 142.8 to 146.2, indicating that a similar, minor fraction of topical ALA is systemically absorbed under both dosing regimens. Systemic PpIX exposure after administration of either dose of BF-200 ALA was equally minimal. Application site skin reactions were treatment area size-related, albeit transient and consistent with the known safety profile of BF-200 ALA.
基于纳米乳的 10%盐酸氨基酮戊酸（ALA）凝胶 BF-200 ALA 优化了其活性成分的表皮穿透性，已获批准用于美国和欧洲的光动力疗法（PDT）治疗光化性角化病。为了描述 PDT 时皮肤应用的全身吸收情况，在 2 项严重光化性角化病患者的最大使用量药代动力学试验（MUsT）中分析了 ALA 和其关键活性代谢物原卟啉 IX（PpIX）。这 2 项 MUsT 的主要目的均为评估单次 PDT 治疗后 ALA 和 PpIX 的基线调整后血浆浓度-时间曲线，治疗时在面部应用 2 g（1 管）BF-200 ALA（MUsT-1）或在面部/头皮或身体外周应用 6 g（3 管）BF-200 ALA（MUsT-2），剂量分别为 20 或 60 cm。所有 PDT 均采用约 635nm 波长的红光进行。同时记录安全性和耐受性以及药代动力学。在这两项 MUsT 中，ALA 血浆浓度均短暂升高，最大浓度约为内源性基线的 2.5 至 3.3 倍，达峰时间约为给药后 3 小时。随后，血浆水平在给药后 10 小时内恢复至基线。在从零时到最后一个采样时间点（浓度等于或高于定量下限）的基线调整后血浆浓度-时间曲线下，总基线调整后平均面积在 142.8 至 146.2 之间，表明在两种剂量方案下，局部 ALA 被系统吸收的相似的、较小的比例。给予 BF-200 ALA 任一剂量后，系统 PpIX 暴露量同样极小。应用部位皮肤反应与治疗区域大小相关，但为一过性，与 BF-200 ALA 的已知安全性特征一致。
