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수종의 광독성 약물투여 후 시간에 따른 피부농도 및 최소 광독량에 관한 연구

Issue Date
1990
Description
의학과/박사
Abstract
[한글] 광화학요법(photochemotherapy)은 광과민성 약물인 psoralen과 장파장의 자외선 A에 의해서 생기는 광독성 반응을 이용하여 여러가지 피부질환에 효과를 나타내는 치료법으로 정의된다. 광화학요법의 치료원리는 반복적으로 제한된 광독성 반응을 일으켜서 피부질환을 치료하는 것이다. 실제 광화학요법을 시행하는데는 투여하는 광독성 약물의 종류, 조사하는 자외선의 파장과 양, 광독성 약물에 대한 반응의 개인에 따른 민감도의 차이 및 피부질환의 종류 등이 치료효과에 영향을 미칠 수 있다. 그러나 치료에 영향을 미치는 주된 3가지 요소는 광화학 반응이 일어나는 부위인 피부에서의 광독성 약물의 농도, 피부에 도달하 는 자외선의 양, 광독성 약물과 자외선의 상호작용에 의한 내부 반응의 정도로서 이들 요소가 치료효과에 중대한 영향을 주게된다. 광선의 양과 파장은 조절이 가능하고, 내부에서 일어나는 광화학 반응은 인위적 조절이 불가능하므로 광화학 반응에 직접적인 영향을 주는 광독성 약물의 피부농도가 가장 중요할 것으로 생각된다. 또한 광화학요법시 나타나는 부작용으로 생각되는 홍반의 정도를 예상하기 위하여 광독성 약물 각각에 따라서 최소 광독량을 측정하여 치료의 기준으로 삼을 수 있다. 따라서 본 연구자는 피부의 광독성 약물농도와 광독성 반응 측정에 가장 유용한 동물 모델로 알려져 있는 guineapig을 이용하여 8-methoxypsoralen(8-MOP), 5-methoxypsoralen (5-MOP) 및 methylpsoralen(TMP)을 경구투여, 복강내 투여 흑은 목욕시킨 후 시간 경과에 따라 각 광독성 약물의 피부 약물농도를 측정하고, 아울러 자외선 A를 조사한 후 최소 광독량의 변화를 연구하여 세가지 약물을 상호 비교함으로써 약물의 종류에 따른 피부농도와 최소 광독량의 차이를 규명하고 실험에 착수하여 다음과 같이 결과를 얻었다. 1. 광독성 약물 경구투여 후 측정한 피부 약물농도는 1시간 30분에 최고 농도에 도달하였으며 8-MOP이 5-MOP의 3.7배로 가장 높았고 TMP의 농도는 측정되지 않았다. 2. 광독성 약물 복강내 투여 후 측정한 피부 약물농도는 30분에 최고 농도에 도달 하였으며 8-MOP이 5-MOP보다 약간 높았고 TMP의 농도는 측정되지 않았다. 3. 광독성 약물 용액에 10분간 목욕 후 측정한 피부 약물농도는 목욕 직후가 가장 높았으며5-MOP이 8-MOP자 TMP에 비하여 의의있게 높았다. 4. 광독성 약물 경구투여 후 측정한 최소 광독량은 1시간 30분에 최저였으며 8-MOP이 5-MOP의 l/8, TMP의 1/24로 광독성 반응이 가장 강했으며 피부 약물농도가 최고에 도달하는 시간인 1시간 30분과 일치하였다. 5. 광독성 약물 복강내 투여 후 측정한 최소 광독량은 30분에 최저였으며 8-MOP이 5-MOP의 l/l.3, TMP의 l/5.7로 광독성 반응이 가장 강했으며 이는 피부 약물농도가 최고에 도달하는 시간인 30분과 일치하였다. 6. 광독성 약물 총액에 10분간 목욕 후 측정한 최소 광독량은 15분 후에 최저였으며 8-MOP과 TMP간에는 차이가 없었으나 5-MOP이 8-MOP 및 TMP보다 높았다. 이상의 결과로 건선의 치료에는 피부 약물농도가 높으며 광독성 반응이 큰 8-MOP을 사용하고 백반증 등의 치료에는 피부 약물농도가 비교적 낮으며 광독성 반응이 적은 5-MOP이나 TMP를 사용하는 것이 좋을 것으로 생각된다. 따라서 피부질환의 종류, 피부병변 및 투여방법에 따라 알맞는 광독성 약물을 선택하는 것이 좋을 것으로 사료된다. The Skin Concentratien and Minimal Phototoxic Dose Following Administration of Phototoxic Drugs as a Function of Time Moo Yon Cho Department of Medical science The Graduate School, Yonsei University (Directed by Professor Yoon-Kee Par, M.D., Ph.D.) Psoralen photochemotherapy(PUVA)is defined as a treatment that depends on the interaction of a photosensitizing substance, psoralen, and long wave ultraviolet(UVA) radiation that results in therapeutically beneficial effects. The rationale of its use is t0 clear skin disease by repeated controlled phototoxic reactions. The efficacy of PUVA depends on the drug, the UVA dose and wave length, the individual sensitivity to the phototoxic reaction and on the disease to be treated. However, the major factor is the amount of psoralen at the site of photochemical reaction in skin. The most striking feature of acute phototoxicity due to psoralens is delayed erythema. Under appropriate conditions of exposure and dosage, edema and blistering may also be present. Despite the extensive experiences which have now accumulated in the use of PUVA, the relationship between the therapeutic response and phototoxicity as it occurs in normal skin is not established. Comparative data on different psoralen molecules and their skin sensitizing ability are required. From studies on the skin concentration and minimal phototoxic dose following oral administration, intraperitoneal administration, bath of phototoxic drugs as a function of time, the following results are obtained. 1. The skirt concentration of phototoxic drugs after oral administration peaked at 1.5 hours, and the concentration of 8-methoxypsoralen(8-MOP) was 3.7 times greater than that of 5-methoxypsorale75-MOP). The skin concentration of 4,5', 8-trimethylpsoralen(TMP) was not detected in this study (limit of sensitivity 5ng/g). 2. The skin concentration of phototoxic drugs after intraperitoneal administration peaked at 30 minutes, and the concentration of 8-MOP was slightly greater than that of 5-MOP. The skin concentration of TMP was not detected in this study(limit of sensitivity 5ng/g). 3. The skin concentration of phototoxic drugs after bathing peaked immediately after bathing, and the skin concentration of phototoxic drugs after bathing decreased in the order of 5-MOP, TMP, and 8-MOP. 4. The minimal phototoxic dose of pnototoxic drugs after oral administration was lowest at 1.5 hours, and the minimal phototoxic dose of 8-MOP was 8 times less than 5-MOP, 24 times less than TMP. The phototoxicity of 8-MOP after oral administration was strongest. The time of lowest phototexic dose and highest skin concentration was the same. 5. The minimal phototoxic dose of phototoxic drugs after intraperitoneal administration was lowest at 30minutes, and the minimal phototoxic dose of 8-MOP was 1.3 times less than 5-MOP, 5.7 times less than TMP. The phototoxicity of 8-MOP after intraperitoneal administration was strongest. The time of lowest phototoxic dose and highest skin concentration was same. 6. The minimal phototoxic dose of phototoxic drugs after bathing was lowest at 15 minutes. The minimal phototoxic doses of 8-MOP and TMP were not significantly different but were significantly lower than that of 5-MOP. Based on these results, 8-MOP, which is more phototoxic and whose skin concentration is higher, is suitable for treatment of psoriasis; and 5-MOP and TMP, which are less phototoxic and whose skin concentrations are lower, are suitable for treatment of vitiligo. Furthermore, the results indicate that the proper phototoxic drug should be selected according to the skin disease to be treated, type of skin lesion and the route of administration.
[영문] Psoralen photochemotherapy(PUVA)is defined as a treatment that depends on the interaction of a photosensitizing substance, psoralen, and long wave ultraviolet(UVA) radiation that results in therapeutically beneficial effects. The rationale of its use is t0 clear skin disease by repeated controlled phototoxic reactions. The efficacy of PUVA depends on the drug, the UVA dose and wave length, the individual sensitivity to the phototoxic reaction and on the disease to be treated. However, the major factor is the amount of psoralen at the site of photochemical reaction in skin. The most striking feature of acute phototoxicity due to psoralens is delayederythema. Under appropriate conditions of exposure and dosage, edema and blistering may also be present. Despite the extensive experiences which have now accumulated in the use of PUVA, the relationship between the therapeutic response and phototoxicity as it occurs in normal skin is not established. Comparative data on different psoralen molecules and their skin sensitizing ability are required. From studies on the skin concentration and minimal phototoxic dose following oral administration, intraperitoneal administration, bath of phototoxic drugs as a function of time, the following results are obtained. 1. The skirt concentration of phototoxic drugs after oral administration peaked at 1.5 hours, and the concentration of 8-methoxypsoralen(8-MOP) was 3.7 times greater than that of 5-methoxypsorale75-MOP). The skin concentration of 4,5', 8-trimethylpsoralen(TMP) was not detected in this study (limit of sensitivity 5ng/g). 2. The skin concentration of phototoxic drugs after intraperitoneal administration peaked at 30 minutes, and the concentration of 8-MOP was slightly greater than that of 5-MOP. The skin concentration of TMP was not detected in this study(limit of sensitivity 5ng/g). 3. The skin concentration of phototoxic drugs after bathing peaked immediately after bathing, and the skin concentration of phototoxic drugs after bathing decreased in the order of 5-MOP, TMP, and 8-MOP. 4. The minimal phototoxic dose of pnototoxic drugs after oral administration was lowest at 1.5 hours, and the minimal phototoxic dose of 8-MOP was 8 times less than 5-MOP, 24 times less than TMP. The phototoxicity of 8-MOP after oral administration was strongest. The time of lowest phototexic dose and highest skin concentration was the same. 5. The minimal phototoxic dose of phototoxic drugs after intraperitoneal administration was lowest at 30minutes, and the minimal phototoxic dose of 8-MOP was 1.3 times less than 5-MOP, 5.7 times less than TMP. The phototoxicity of 8-MOP after intraperitoneal administration was strongest. The time of lowest phototoxic dose and highest skin concentration was same. 6. The minimal phototoxic dose of phototoxic drugs after bathing was lowest at 15 minutes. The minimal phototoxic doses of 8-MOP and TMP were not significantly different but were significantly lower than that of 5-MOP. Based on these results, 8-MOP, which is more phototoxic and whose skin concentration is higher, is suitable for treatment of psoriasis; and 5-MOP and TMP, which are less phototoxic and whose skin concentrations are lower, are suitable for treatment of vitiligo. Furthermore, the results indicate that the proper phototoxic drug should be selected according to the skin disease to be treated, type of skin lesion and the route of administration.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/117030
Appears in Collections:
2. 학위논문 > 1. College of Medicine (의과대학) > 박사
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