Skin necrosis due to photodynamic action of benzoporphyrin depends on circulating rather than tissue drug levels:: Implications for control of photodynamic therapy
Skin necrosis due to photodynamic action of benzoporphyrin depends on circulating rather than tissue drug levels:: Implications for control of photodynamic therapy
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DOI：
10.1111/j.1751-1097.1998.tb02516.x
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发表时间：
1998-10-01
影响因子：
3.3
通讯作者：
Kollias, N
中科院分区：
文献类型：
--
作者：
Lin, GC;Tsoukas, ML;Kollias, N
在理想情况下，异常组织的光动力疗法（PDT）将可靠地保护周围的正常组织。正常的组织反应设定了光和药物剂量测定的极限。在静脉输注光敏剂苯并卟啉衍生物单酸环A（BPD-MA）Verteporfin（R）后，在正常皮肤中测量坏死阈值通量（TFN），其为药物剂量（0.25-2.0 mg/kg）、照射波长（458和690 mm）和给药与照射之间的时间间隔（0-5 h）的函数。测定血浆和皮肤组织中的BPDMA水平，以阐明TFN、药物动力学和生物分布之间的关系。正常皮肤的PDT反应是高度可重复的。458和690 nm波长的TFN几乎相同，皮肤响应的估计量子效率在这两个波长处相等。皮肤光毒性（以1/TFN量化）与血浆药代动力学而非组织药代动力学密切相关，并且与血浆药物浓度呈二次依赖性，而与给药剂量或药物与光照之间的时间间隔无关。这项研究强烈表明，在光治疗的时间循环药物水平的非侵入性测量将是重要的，为PDT与脂质体BPD-MA，血管光敏剂设置最佳的光剂量。
In an ideal world, photodynamic therapy (PDT) of abnormal tissue would reliably spare the surrounding normal tissue. Normal tissue responses set the limits for light and drug dosimetry. The threshold fluence for necrosis (TFN) was measured in normal skin following intravenous infusion with a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA) Verteporfin(R) as a function of drug dose (0.25-2.0 mg/kg), wavelength of irradiation (458 and 690 mm) and time interval (0-5 h) between drug administration and irradiation. The BPDMA levels were measured in plasma and skin tissue to elucidate the relationship between TFN, drug kinetics and biodistribution. The PDT response of normal skin was highly reproducible. The TFN for 458 and 690 mn wavelengths was nearly identical and the estimated quantum efficiency for skin response was equal at these two wavelengths. Skin phototoxicity, quantified in terms of 1/TFN, closely correlated with the plasma pharmacokinetics rather than the tissue pharmacokinetics and was quadratically dependent on the plasma drug concentration regardless of the administered drug dose or time interval between drug and light exposure. This study strongly suggests that noninvasive measurements of the circulating drug level at the time of light treatment will be important for setting optimal light dosimetry for PDT with liposomal BPD-MA, a vascular photosensitizer.