Alaiti S, Kang S, Fiedler V C, Ellis C N, Spurlin D V, Fader D, Ulyanov G, Gadgil S D, Tanase A, Lawrence I, Scotellaro P, Raye K, Bekersky I
Department of Dermatology, University of Illinois at Chicago, 60612, USA.
J Am Acad Dermatol. 1998 Jan;38(1):69-76. doi: 10.1016/s0190-9622(98)70541-9.
Tacrolimus is a potent immunosuppressant used in organ transplant recipients; an ointment formulation is being developed as a therapeutic agent for atopic dermatitis.
Our purpose was to define the pharmacokinetics and evaluate tacrolimus 0.3% ointment as therapy for moderate to severe atopic dermatitis.
Thirty-nine patients, 5 to 75 years of age, received 14 applications over 8 days. Serial blood samples were collected on days 1 and 8, with predose samples collected on days 2 through 7. Overall response and signs/symptoms were rated daily on days 1 through 11. Incidence of adverse events and laboratory profile were determined.
Mean area under the curve (0.9 to 42.5 ng x hr/ml) was highly variable and appeared to be related to size of application area. No systemic accumulation of tacrolimus was observed. Comparison to historical intravenous data indicates that absolute bioavailability of topical tacrolimus was less than 0.5%. Ninety-five percent of patients showed at least good improvement. All adverse events were transient. Burning was the most common application site adverse event and vasodilatation ("flushing/warmth") was the most common nonapplication site adverse event. No drug-related changes in laboratory profile were observed.
The results of this study suggest that tacrolimus 0.3% ointment may be a safe and effective therapy for atopic dermatitis.
他克莫司是一种用于器官移植受者的强效免疫抑制剂；一种软膏制剂正在开发中，用作特应性皮炎的治疗药物。
我们的目的是确定他克莫司0.3%软膏治疗中重度特应性皮炎的药代动力学并对其进行评估。
39名年龄在5至75岁之间的患者在8天内接受14次给药。在第1天和第8天采集系列血样，在第2天至第7天采集给药前血样。在第1天至第11天每天对总体反应以及体征/症状进行评分。确定不良事件的发生率和实验室检查结果。
曲线下面积均值（0.9至42.5纳克·小时/毫升）变化很大，似乎与涂抹面积大小有关。未观察到他克莫司的全身蓄积。与既往静脉给药数据比较表明，局部应用他克莫司的绝对生物利用度小于0.5%。95%的患者至少有良好改善。所有不良事件均为短暂性。灼烧是最常见的涂抹部位不良事件，血管扩张（“潮红/发热”）是最常见的非涂抹部位不良事件。未观察到实验室检查结果有与药物相关的变化。
本研究结果提示，他克莫司0.3%软膏可能是治疗特应性皮炎的一种安全有效的疗法。
