Guo Jiun-Wen, Cheng Yu-Pin, Lim Cherng-Jyr, Liu Chih-Yi, Jee Shiou-Hwa
Department of Medical Research, Cathay General Hospital, Taipei 10630, Taiwan.
Department of Dermatology, Cathay General Hospital, Taipei 10630, Taiwan.
Pharmaceutics. 2023 Jul 25;15(8):2016. doi: 10.3390/pharmaceutics15082016.
(1) Background: Human keratinocytes and murine skin express various cytochrome P450 enzymes. These include cytochrome P450 3A4, which may participate in the metabolism of cytochrome P450 3A4 substrate drugs. Desoximetasone, a topical corticosteroid and cytochrome P450 3A4 substrate, is used to treat skin conditions such as skin allergies, atopic dermatitis, and psoriasis. In this study, we aimed to investigate the anti-psoriatic effect of a low dose of desoximetasone by inhibiting cytochrome P450 3A4 metabolism in the epidermis. (2) Methods: Psoriasis-like skin was induced in BALB/c mice via the topical administration of imiquimod. The mice were then topically treated with 0.01-0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient microemulsion, 0.25% commercial desoximetasone ointment, or 0.5 mg/gm clobetasol ointment. (3) Results: The topical application of 0.05% desoximetasone loaded into a cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation restored the imiquimod-induced skin barrier disruption and resulted in fewer severe clinical and pathological features compared with the treatments with 0.25% commercial desoximetasone ointment and 0.5 mg/gm clobetasol ointment. (4) Conclusions: The cytochrome P450 3A4 enzyme inhibitor excipient base emollient formulation improved and prolonged the therapeutic effect of cytochrome P450 3A4 substrate drugs and may be a promising approach for psoriasis treatment.
(1) 背景：人角质形成细胞和鼠皮肤表达多种细胞色素P450酶。这些酶包括细胞色素P450 3A4，其可能参与细胞色素P450 3A4底物药物的代谢。地索奈德是一种外用皮质类固醇和细胞色素P450 3A4底物，用于治疗皮肤过敏、特应性皮炎和银屑病等皮肤疾病。在本研究中，我们旨在通过抑制表皮中的细胞色素P450 3A4代谢来研究低剂量地索奈德的抗银屑病作用。(2) 方法：通过局部应用咪喹莫特在BALB/c小鼠中诱导银屑病样皮肤。然后，将小鼠局部用负载于细胞色素P450 3A4酶抑制剂辅料基质润肤微乳中的0.01 - 0.05%地索奈德、0.25%市售地索奈德软膏或0.5mg/g氯倍他索软膏进行治疗。(3) 结果：与用0.25%市售地索奈德软膏和0.5mg/g氯倍他索软膏治疗相比，局部应用负载于细胞色素P450 3A4酶抑制剂辅料基质润肤制剂中的0.05%地索奈德可恢复咪喹莫特诱导的皮肤屏障破坏，并导致严重的临床和病理特征减少。(4) 结论：细胞色素P450 3A4酶抑制剂辅料基质润肤制剂改善并延长了细胞色素P450 3A4底物药物的治疗效果，可能是一种有前途的银屑病治疗方法。
