Department of Dermatology, Center for Dermatology Research, Wake Forest University School of Medicine, 475 Vine St, Winston-Salem, NC, 27101, USA.
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Clin Pharmacokinet. 2024 Feb;63(2):137-153. doi: 10.1007/s40262-023-01341-4. Epub 2024 Jan 27.
Psoriasis is a common inflammatory immune disorder due to chronic activation of the adaptive and innate immune responses. Therapies for psoriasis target reducing inflammatory cytokines such as tumor necrosis factor-alpha, interleukin-17, and interleukin-22. Patients with inflammatory disorders have reduced metabolism by cytochrome P450 enzymes in the liver. The pharmacokinetic and pharmacodynamic changes due to psoriasis also have an impact on reaching therapeutic concentrations of the drug. Pharmacokinetic and pharmacodynamic data help determine the safety and clinical considerations necessary when utilizing drugs for plaque psoriasis. A literature search was performed on PubMed and Ovid MEDLINE for the pharmacokinetic and pharmacodynamic data of oral therapies and biologics utilized for moderate-to-severe plaque psoriasis. The findings from the literature search were organized into two sections: oral therapies and biologics. The pharmacokinetic and pharmacodynamic parameters in healthy patients, patients with psoriasis, and special populations are discussed in each section. The oral therapies described in this review include methotrexate, cyclosporine, apremilast, tofacitinib, and deucravacitinib. Biologics include tumor necrosis factor-alpha inhibitors, interleukin-17 inhibitors, ustekinumab, and interleukin-23 inhibitors. Clinical considerations for these therapies include drug toxicities, dosing frequency, and anti-drug antibodies. Methotrexate and cyclosporine have a risk for hepatoxicity and renal impairment, respectively. Moreover, drugs metabolized via cytochrome P450, including tofacitinib and apremilast have decreased clearance in patients with psoriasis, requiring dose adjustments. Patients treated with therapies such as adalimumab can develop anti-drug antibodies that reduce the long-term efficacy of the drug. Additionally, overweight patients benefit from more frequent dosing to achieve better psoriasis clearance.
银屑病是一种常见的炎症性免疫性疾病，由于适应性和固有免疫反应的慢性激活。银屑病的治疗方法旨在减少炎症细胞因子，如肿瘤坏死因子-α、白细胞介素-17 和白细胞介素-22。患有炎症性疾病的患者肝脏细胞色素 P450 酶的代谢减少。由于银屑病引起的药代动力学和药效学变化也会影响药物达到治疗浓度。药代动力学和药效学数据有助于确定在利用药物治疗斑块状银屑病时的安全性和临床注意事项。在 PubMed 和 Ovid MEDLINE 上对用于中重度斑块状银屑病的口服治疗药物和生物制剂的药代动力学和药效学数据进行了文献检索。从文献检索中得到的结果分为两个部分：口服治疗药物和生物制剂。在每个部分中讨论了健康患者、银屑病患者和特殊人群中的药代动力学和药效学参数。本文综述中描述的口服治疗药物包括甲氨蝶呤、环孢素、阿普米司特、托法替尼和德瓦鲁单抗。生物制剂包括肿瘤坏死因子-α抑制剂、白细胞介素-17 抑制剂、乌司奴单抗和白细胞介素-23 抑制剂。这些治疗药物的临床注意事项包括药物毒性、给药频率和抗药物抗体。甲氨蝶呤和环孢素有肝毒性和肾损害的风险，分别。此外，包括托法替尼和阿普米司特在内的通过细胞色素 P450 代谢的药物在银屑病患者中的清除率降低，需要调整剂量。接受阿达木单抗等治疗的患者可能会产生抗药物抗体，从而降低药物的长期疗效。此外，超重患者受益于更频繁的给药以实现更好的银屑病清除率。
