Tegeder Irmgard, Bräutigam Lutz, Podda Maurizio, Meier Silke, Kaufmann Roland, Geisslinger Gerd, Grundmann-Kollmann Marcella
Pharmazentrum frankfurt, Klinikum der Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany.
Clin Pharmacol Ther. 2002 Mar;71(3):153-61. doi: 10.1067/mcp.2002.121908.
The combination of 8-methoxypsoralen with ultraviolet A exposure (PUVA therapy) is a standard treatment for a variety of dermatoses. The following three variants have been described: oral, bath, or cream PUVA. To achieve optimal therapeutic effects, ultraviolet A irradiation should be performed at the time of maximum photosensitivity, that is, at the time of maximum 8-methoxypsoralen tissue concentrations.
To further specify this point of time, we assessed the concentration-time courses of 8-methoxypsoralen in the skin after oral, bath, and cream administration of 8-methoxypsoralen in a 3-way crossover microdialysis study of 8 healthy subjects.
Tissue concentrations after oral administration of 0.6 or 1 mg/kg 8-methoxypsoralen were low (peak plasma concentration range, 1.7-6.6 ng/ml) compared with topical administration for which maximum concentrations of 200 to 520 ng/ml and 720 to 970 ng/ml were achieved with 0.1% 8-methoxypsoralen cream and 3 mg/L 8-methoxypsoralen bath, respectively. Plasma concentrations after oral 8-methoxypsoralen, however, were up to 1000-fold higher than those found after topical application. With both topical applications, the tissue peak concentration uniformly occurred in the first 20 minutes after the end of the application time. In contrast, the time to reach the tissue peak concentration after oral administration ranged from 1 to 4 hours.
The time course of tissue concentrations corresponds closely with the time course of minimal phototoxic doses found in previous studies. Because tissue concentrations after topical administration of 8-methoxypsoralen (bath and cream) were high compared with plasma concentrations and because they were less variable and occurred at better predictable time points than those after oral administration, we suggest that topical PUVA is superior to systemic PUVA, at least from a pharmacokinetic point of view.
8-甲氧基补骨脂素与紫外线A照射联合应用（光化学疗法）是多种皮肤病的标准治疗方法。已描述了以下三种变体：口服、浴用或乳膏光化学疗法。为实现最佳治疗效果，紫外线A照射应在最大光敏性时进行，即8-甲氧基补骨脂素组织浓度最高时。
为进一步明确这个时间点，我们在一项对8名健康受试者进行的三向交叉微透析研究中，评估了口服、浴用和乳膏给予8-甲氧基补骨脂素后皮肤中8-甲氧基补骨脂素的浓度-时间过程。
口服0.6或1mg/kg 8-甲氧基补骨脂素后的组织浓度较低（血浆峰值浓度范围为1.7-6.6ng/ml），而局部给药时，0.1% 8-甲氧基补骨脂素乳膏和3mg/L 8-甲氧基补骨脂素浴液分别达到了200至520ng/ml和720至970ng/ml的最大浓度。然而，口服8-甲氧基补骨脂素后的血浆浓度比局部应用后高出多达1000倍。两种局部应用时，组织峰值浓度均在应用时间结束后的前20分钟内出现。相比之下，口服给药后达到组织峰值浓度的时间为1至4小时。
组织浓度的时间过程与先前研究中发现的最小光毒性剂量的时间过程密切相关。由于局部给予8-甲氧基补骨脂素（浴用和乳膏）后的组织浓度高于血浆浓度，且其变异性较小，且发生时间点比口服给药更可预测，我们认为至少从药代动力学角度来看，局部光化学疗法优于全身光化学疗法。
